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Objective Methods Results Conclusions Explored the correlation between CD1a expression in recurrence and prognosis of ovarian cancer (OV).The CD1a expression profile in OV, recurrent OV, and normal tissues, as well as corresponding clinical data, were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), and Genotype Tissue Expression (GTEx) databases. Meanwhile, immunohistochemical detection of CD1a expression in normal and OV tissues. Kaplan–Meier curves were plotted to estimate the hazard ratio (HR) of survival in OV. In addition, the correlation between CD1a and immune cells in OV, as well as the CD1a expression profile and corresponding survival time in pan‐cancer were obtained from TCGA database.CD1a was overexpressed in OV and was significantly under‐expressed in recurrent OV (TCGA‐OV, p < 0.0001 and ICGC‐OV, p < 0.0001). CD1a immunohistochemistry is significantly overexpressed in OV compared to normal tissue (p < 0.05). Recurrent OV (ICGC, p < 0.001; GSE17260, p < 0.001; GSE32062, p < 0.05). The prognosis in OV was significantly better when CD1a is overexpressed compared to under‐expressed (HR [low], 1.426: 95% confidence interval [CI], 0.912–2.128; p = 0.050). Meanwhile, the overexpression of CD1a has a better prognosis than low expression in OV and recurrent OV (p = 0.004, HR [low] = 2.462, 95%CI [1.346–4.504] and p = 0.011, HR [low] = 2.199, 95%CI [1.202–4.024]). In addition, CD1a expression was closely correlated with immune cells, the CD8+ T cells, macrophages, and NK cells, while uncharacterized cells were significantly different (p = 2.65e−6, p = 7.52e−13, p = 8.28e−12, and p = 5.89e−8, respectively). Moreover, CD1a expression affected the prognosis in various other cancers.CD1a expression affected the recurrence and prognosis of OV and is closely related to various immune cell levels. [ABSTRACT FROM AUTHOR]

LCH has a distinct site predilection and cytological feature. However, it can cause diagnostic difficulties at unusual sites or deviated cytomorphology. FNAC is a minimally invasive procedure that can be performed in any organ (parotid and thyroid where biopsy is not commonly indicated) and multiple sites/organs simultaneously for diagnosis. FNA sampling can also help with cell block preparation for performing immunohistochemistry and molecular studies if necessary. [ABSTRACT FROM AUTHOR]

Introduction: The endocannabinoid system (ECS), named after the chemical compounds found in the cannabis plant, is a regulatory network of neurotransmitters, receptors, and enzymes that plays crucial roles in skin health and disease. Endogenous ligands of the ECS, called endocannabinoids, have proven to be important regulators of immune responses. One of the most prevalent endocannabinoids, arachidonoylethanolamide (also known as anandamide), is known for its anti-inflammatory effects. Langerhans cells (LCs) are the sole antigen-presenting cells present in the human epidermis. They serve as the first line of defense against pathogens and are essential for the skin’s specific immune responses and play a critical role in maintaining tissue homeostasis; however, little is known about the effect of endocannabinoids on these cells. Our research aimed to provide the connection between monocytederived Langerhans cells (moLCs) and the ECS, shedding light on their collaborative roles in immune homeostasis and inflammation. Methods: Human monocytes were differentiated into moLCs using established protocols. Anandamide was applied during the differentiation process to test its effect on the viability, marker expression, and cytokine production of the cells, as well as in short term treatments for intracellular calcium measurement. TLR ligands applied after the differentiation protocol were used to activate moLCs. The impact of anandamide on the functionality of moLCs was further assessed using differential gene expression analysis of bulk RNA-Seq data, moLC-T cell cocultures, while ELISpot was employed to determine polarization of T cells activated in the aforementioned cocultures. Results: Anandamide did not significantly affect the viability of moLCs up to 10 µM. When applied during the differentiation process it had only a negligible effect on CD207 expression, the prototypic marker of LCs; however, there was an observed reduction in CD1a expression by moLCs. Anandamide had no significant effects on the maturation status of moLCs, nor did it affect the maturation induced by TLR3 and TLR7/8 agonists. MoLCs differenti ated in the presence of anandamide did however show decreased production of CXCL8, IL-6, IL-10 and IL-12 cytokines induced by TLR3 and TLR7/8 activation. Anandamide-treated moLCs showed an increased capability to activate naïve T cells; however, not to the level seen with combined TLR agonism. RNA sequencing analysis of moLCs differentiated with anandamide showed modest changes compared to control cells but did reveal an inhibitory effect on oxidative phosphorylation specifically in activated moLCs. Anandamide also promoted the polarization of naïve T cells towards a Th1 phenotype. Discussion: Our results show that anandamide has nuanced effects on the differentiation, maturation, cytokine secretion, metabolism and function of activated moLCs. Among these changes the decrease in CD1a expression on moLCs holds promise to selectively dampen inflammation induced by CD1a restricted T cells, which have been implicated as drivers of inflammation in common inflammatory skin conditions such as psoriasis, atopic dermatitis and contact dermatitis. [ABSTRACT FROM AUTHOR]

Abstract is missing (Quiz)

Houxi Xu,1,2,&ast; Hongqun Zhang,1,3,&ast; Songxian Sun,2,&ast; Jingyuan Zhang,2 Jiege Huo,1,3 Chunxiang Zhou2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing, University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxiang Zhou, School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email chunxiangzhou@njucm.edu.cn Jiege Huo, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Email huojiege@jsatcm.comBackground: The CD1A gene, a key component of the human immune system and part of the CD1 family, plays a crucial role in presenting lipid antigens to T cells. Abnormal CD1A expression is associated with various immune-related diseases and tumors. However, the biological function of CD1A in COAD is unclear.Methods: Multiple databases were systematically employed to conduct an analysis of CD1A expression in pan-cancer and COAD, along with its clinical-pathological features. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of CD1A were performed using the ‘clusterProfiler’ package. The Protein-protein interaction (PPI) analysis of CD1A was used the STRING database. Additionally, TIMER and ssGSEA tools were used to explore the relationship between CD1A expression in COAD and immune cell infiltration. The study also investigated the association between CD1A expression and N6-methyladenosine (m6A) modification genes in the TCGA COAD cohort and constructed a CD1A-centric competing endogenous RNA (ceRNA) regulatory network.Results: CD1A displays varying expression levels in various tumors, including COAD, and is closely linked to clinical-pathological characteristics. GO analysis suggests that CD1A plays a role in important processes like antigen processing and presentation, leukocyte-mediated immunity, and lymphocyte-mediated immunity. KEGG analysis identifies CD1A’s involvement in key pathways such as the Chemokine signaling pathway and Cytokine-cytokine receptor interaction. PPI analysis highlights CD1A’s interactions with CD207, CD1C, CD1E, FOXP3, and ITGB2. ssGSEA analysis indicates a significant relationship between CD1A expression and the infiltration of various immune cells in COAD. Significant associations were found between CD1A and m6A modification genes in COAD. Furthermore, a CD1A-centered ceRNA regulatory network has been constructed.Conclusion: CD1A emerges as a potential biomarker for the diagnosis and treatment of COAD, showing a strong association with tumor immune infiltration, m6A modification, and the ceRNA network.Keywords: CD1A, COAD, immune infiltration, m6A, ceRNA

Introduction: Exosome-enriched small extracellular vesicles (sEVs) are nanosized organelles known to participate in long distance communication between cells, including in the skin. Atopic dermatitis (AD) is a chronic inflammatory skin disease for which filaggrin (FLG) gene mutations are the strongest genetic risk factor. Filaggrin insufficiency affects multiple cellular function, but it is unclear if sEV-mediated cellular communication originating from the affected keratinocytes is also altered, and if this influences peptide and lipid antigen presentation to T cells in the skin. Methods: Available mRNA and protein expression datasets from filaggrininsufficient keratinocytes (shFLG), organotypic models and AD skin were used for gene ontology analysis with FunRich tool. sEVs secreted by shFLG and control shC cells were isolated from conditioned media by differential centrifugation. Mass spectrometry was carried out for lipidomic and proteomic profiling of the cells and sEVs. T cell responses to protein, peptide, CD1a lipid antigens, as well as phospholipase A2-digested or intact sEVs were measured by ELISpot and ELISA. Results: Data analysis revealed extensive remodeling of the sEV compartment in filaggrin insufficient keratinocytes, 3D models and the AD skin. Lipidomic profiles of shFLGsEV showed a reduction in the long chain (LCFAs) and polyunsaturated fatty acids (PUFAs; permissive CD1a ligands) and increased content of the bulky headgroup sphingolipids (non-permissive ligands). This resulted in a reduction of CD1a-mediated interferon-g T cell responses to the lipids liberated from shFLGgenerated sEVs in comparison to those induced by sEVs from control cells, and an increase in interleukin 13 secretion. The altered sEV lipidome reflected a generalized alteration in the cellular lipidome in filaggrin-insufficient cells and the skin of AD patients, resulting from a downregulation of key enzymes implicated in fatty acid elongation and desaturation, i.e., enzymes of the ACSL, ELOVL and FADS family. Discussion: We determined that sEVs constitute a source of antigens suitable for CD1a-mediated presentation to T cells. Lipids enclosed within the sEVs secreted on the background of filaggrin insufficiency contribute to allergic inflammation by reducing type 1 responses and inducing a type 2 bias from CD1a-restricted T cells, thus likely perpetuating allergic inflammation in the skin. [ABSTRACT FROM AUTHOR]

IntroductionThe endocannabinoid system (ECS), named after the chemical compounds found in the cannabis plant, is a regulatory network of neurotransmitters, receptors, and enzymes that plays crucial roles in skin health and disease. Endogenous ligands of the ECS, called endocannabinoids, have proven to be important regulators of immune responses. One of the most prevalent endocannabinoids, arachidonoylethanolamide (also known as anandamide), is known for its anti-inflammatory effects. Langerhans cells (LCs) are the sole antigen-presenting cells present in the human epidermis. They serve as the first line of defense against pathogens and are essential for the skin’s specific immune responses and play a critical role in maintaining tissue homeostasis; however, little is known about the effect of endocannabinoids on these cells. Our research aimed to provide the connection between monocyte-derived Langerhans cells (moLCs) and the ECS, shedding light on their collaborative roles in immune homeostasis and inflammation.MethodsHuman monocytes were differentiated into moLCs using established protocols. Anandamide was applied during the differentiation process to test its effect on the viability, marker expression, and cytokine production of the cells, as well as in short term treatments for intracellular calcium measurement. TLR ligands applied after the differentiation protocol were used to activate moLCs. The impact of anandamide on the functionality of moLCs was further assessed using differential gene expression analysis of bulk RNA-Seq data, moLC-T cell cocultures, while ELISpot was employed to determine polarization of T cells activated in the aforementioned cocultures.ResultsAnandamide did not significantly affect the viability of moLCs up to 10 µM. When applied during the differentiation process it had only a negligible effect on CD207 expression, the prototypic marker of LCs; however, there was an observed reduction in CD1a expression by moLCs. Anandamide had no significant effects on the maturation status of moLCs, nor did it affect the maturation induced by TLR3 and TLR7/8 agonists. MoLCs differentiated in the presence of anandamide did however show decreased production of CXCL8, IL-6, IL-10 and IL-12 cytokines induced by TLR3 and TLR7/8 activation. Anandamide-treated moLCs showed an increased capability to activate naïve T cells; however, not to the level seen with combined TLR agonism. RNA sequencing analysis of moLCs differentiated with anandamide showed modest changes compared to control cells but did reveal an inhibitory effect on oxidative phosphorylation specifically in activated moLCs. Anandamide also promoted the polarization of naïve T cells towards a Th1 phenotype.DiscussionOur results show that anandamide has nuanced effects on the differentiation, maturation, cytokine secretion, metabolism and function of activated moLCs. Among these changes the decrease in CD1a expression on moLCs holds promise to selectively dampen inflammation induced by CD1a restricted T cells, which have been implicated as drivers of inflammation in common inflammatory skin conditions such as psoriasis, atopic dermatitis and contact dermatitis.

Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT. [ABSTRACT FROM AUTHOR]

Oral cancer decreases quality of life despite timely medical management. The carcinogens in tobacco products and their role in tumorigenesis are well documented. Langerhans cells (LCs) are a subset of antigen-presenting cells (APCs) that monitor the tumor microenvironment and engulf carcinogens and foreign bodies. We investigated the distribution and size of LCs and their relation to the mode of tobacco consumption and clinical outcome in patients with buccal carcinoma. We recruited patients with oral cancer who were scheduled for tumor excision and men with urethral stricture undergoing substitution urethroplasty using buccal mucosa. Normal and tumor-adjacent tissues were stained with CD1a antibody. The distribution and mean diameter of 100 LCs/patient were determined. We found significantly smaller LCs in patients who chewed only tobacco compared to those who consumed tobacco by other means. The size of LCs decreased significantly with progressive stages of malignant disease. We found that patients with larger LCs survived longer than those with smaller LCs during an average follow-up of 24 months. We suggest a relation between the size of LCs and clinical outcomes in patients with buccal carcinoma. [ABSTRACT FROM AUTHOR]

IntroductionExosome-enriched small extracellular vesicles (sEVs) are nanosized organelles known to participate in long distance communication between cells, including in the skin. Atopic dermatitis (AD) is a chronic inflammatory skin disease for which filaggrin (FLG) gene mutations are the strongest genetic risk factor. Filaggrin insufficiency affects multiple cellular function, but it is unclear if sEV-mediated cellular communication originating from the affected keratinocytes is also altered, and if this influences peptide and lipid antigen presentation to T cells in the skin.MethodsAvailable mRNA and protein expression datasets from filaggrin-insufficient keratinocytes (shFLG), organotypic models and AD skin were used for gene ontology analysis with FunRich tool. sEVs secreted by shFLG and control shC cells were isolated from conditioned media by differential centrifugation. Mass spectrometry was carried out for lipidomic and proteomic profiling of the cells and sEVs. T cell responses to protein, peptide, CD1a lipid antigens, as well as phospholipase A2-digested or intact sEVs were measured by ELISpot and ELISA.ResultsData analysis revealed extensive remodeling of the sEV compartment in filaggrin insufficient keratinocytes, 3D models and the AD skin. Lipidomic profiles of shFLGsEV showed a reduction in the long chain (LCFAs) and polyunsaturated fatty acids (PUFAs; permissive CD1a ligands) and increased content of the bulky headgroup sphingolipids (non-permissive ligands). This resulted in a reduction of CD1a-mediated interferon-γ T cell responses to the lipids liberated from shFLG-generated sEVs in comparison to those induced by sEVs from control cells, and an increase in interleukin 13 secretion. The altered sEV lipidome reflected a generalized alteration in the cellular lipidome in filaggrin-insufficient cells and the skin of AD patients, resulting from a downregulation of key enzymes implicated in fatty acid elongation and desaturation, i.e., enzymes of the ACSL, ELOVL and FADS family.DiscussionWe determined that sEVs constitute a source of antigens suitable for CD1a-mediated presentation to T cells. Lipids enclosed within the sEVs secreted on the background of filaggrin insufficiency contribute to allergic inflammation by reducing type 1 responses and inducing a type 2 bias from CD1a-restricted T cells, thus likely perpetuating allergic inflammation in the skin.

Indeterminate dendritic cell tumor (IDCT) is rare histiocytic tumor characterized by the proliferation of indeterminate dendritic cells. It is more often diagnosed in middle-aged people, in approximately equal proportions in men and women. The etiology of IDCT is unknown. Differential diagnosis is carried out with other diseases that mimic IDCT and is important for determining treatment tactics. The present paper presents a clinical case of IDCT in a 48-year-old man. The similarity of skin manifestations in IDCT with other cutaneous pathologies requires an immunohistochemical study of the affected areas for CD1a, CD68, S100, Langerin expression evaluation as well as the presence of Birbeck's granules visualization. Routine histological examination does not sufficient for correct IDCT diagnostics.

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC. [ABSTRACT FROM AUTHOR]

Introduction: Langerhans cells (LCs) are dendritic cells (DCs) of the epithelium which play a role in an array of oral lesions from gingivitis to oral cancer. Oral submucous fibrosis (OSMF), a potentially malignant disorder (PMD), is an insidious chronic disease with juxta-epithelial inflammatory changes leading to fibrosis. LCs may play a part in the ongoing inflammatory dysregulation of OSMF. Objective: The study was aimed at elucidating the distribution of LCs in varying grades of OSMF. Materials and Methods: A retrospective study using 18 cases of OSMF, graded using haematoxylin and eosin (H&E)-stained section. Immunohistochemistry was performed using polyclonal anti-CD1a antibodies to identify LCs in six cases of normal tissue and 18 samples of OSMF. The distribution of LCs among the various grades and normal mucosa analysed using Student's t-test. Results: LC population in the OSMF was significantly higher when compared to the normal epithelium (p < 0.001). Within the grades, the advanced stage had more LCs than the other stages. Conclusion: The increase in LCs might indicate the role of antigenic exposure in turn leading to cell-mediated immunity in OSMF. Thus, the fibrosis in OSMF might have a direct link to LCs. [ABSTRACT FROM AUTHOR]

In addition to serving as the main physical barrier with the outside world, human skin is abundantly infiltrated with resident αβ T cells that respond differently to self, infectious, microbiome, and noxious stimuli. To study skin T cells during infection and inflammation, experimental biologists track T‐cell surface phenotypes and effector functions, which are often interpreted with the untested assumption that MHC proteins and peptide antigens drive measured responses. However, a broader perspective is that CD1 proteins also activate human T cells, and in skin, Langerhans cells (LCs) are abundant antigen presenting cells that express extremely high levels of CD1a. The emergence of new experimental tools, including CD1a tetramers carrying endogenous lipids, now show that CD1a‐reactive T cells comprise a large population of resident T cells in human skin. Here, we review studies showing that skin‐derived αβ T cells directly recognize CD1a proteins, and certain bound lipids, such as contact dermatitis allergens, trigger T‐cell responses. Other natural skin lipids inhibit CD1a‐mediated T‐cell responses, providing an entry point for the development of therapeutic lipids that block T‐cell responses. Increasing evidence points to a distinct role of CD1a in type 2 and 22 T‐cell responses, providing new insights into psoriasis, contact dermatitis, and other T‐cell‐mediated skin diseases. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by abnormal proliferation of Langerhans cells infiltrating various organs, resulting in organ dysfunction. In some patients, the BRAFV600E mutation can be detected. Histopathology reveals a substantial proliferation of Langerhans cells, contributing significantly to the diagnosis of LCH. Clinical manifestations vary depending on the affected tissues or organs. LCH occurs less frequently in adults than in children, and clinicians often lack sufficient awareness of this disease, making it susceptible to misdiagnosis. In this report, a case of liver injury caused by Langerhans cell invasion is presented, as confirmed by a liver biopsy in adults.

Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is reported less frequently in adults than in children. The most common site of involvement in adults is the bone, accounting for 30-50% of cases. The gastrointestinal tract is very rare, accounting for approximately 2%. We present a case of Langerhans cell histiocytosis that simultaneously invaded multiple organs, including the stomach and colon, in an adult. A 37-year-old woman with no underlying disease complained of chest discomfort and a palpable right submandibular mass. A right Level II neck mass and mediastinal LN enlargement were confirmed on the pharynx and chest CT scan. Multiple subepithelial masses with central ulceration and erosion were observed in the corpus and fundus on the esophagogastroduodenoscopy and in the right colon on the colonoscopy. The histopathology findings were the same in each tissue biopsied from the stomach, colon, and right neck lymph nodes. Langerhans cells with classical reniform nuclei and prominent eosinophils invaded the normal glands, and S100 and CD1a were positive in the immunohistochemical stain. Gastrointestinal involvement of LCH in adults is rare, asymptomatic,and can involve multiple digestive organs simultaneously, so upper endoscopy and colonoscopy should be considered for a diagnosis.

Simple Summary: A significant proportion of patients with oral squamous cell carcinoma do not have the typical risk factors of smoking and alcohol consumption in their medical history. Clinical and immunohistochemical studies have shown that patients with oral squamous cell carcinoma who have never smoked or drunk alcohol are more likely to be female and older at the time of diagnosis. In addition, this type of patient has a more frequent history of oral potentially malignant disorders and a better prognosis. There are also differences in the site of origin of the carcinoma between never-smokers/never-drinkers and smokers/drinkers. In addition, we were able to show that oral squamous cell carcinoma in never-smokers/never-drinkers has an independent immunologic microenvironment. These results may help to improve the treatment of oral squamous cell carcinoma in never-smokers/never-drinkers. The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers/never-drinkers and smokers/drinkers. Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers/drinkers and never-smokers/never-drinkers. Associations of smoking/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers/never-drinkers was associated with the female gender (p < 0.001). Never-smokers/never-drinkers were older at diagnosis than smokers/drinkers (p < 0.001). Never-smokers/never-drinkers had more tumors in the maxilla, mandible, and tongue (p < 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers/never-drinkers (p < 0.001). Perineural invasion was more common in smokers/drinkers (p = 0.039). Never-smoking/never-drinking was associated with better overall survival (p = 0.004) and disease-specific survival (p = 0.029). High CD4+ T cell infiltration was associated with never-smoking/never-drinking (p = 0.008). Never-smokers/never-drinkers also showed increased CD8+ T cell infiltration (p = 0.001) and increased FoxP3+ Treg infiltration (p = 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking/never drinking (p = 0.005). To conclude oral squamous cell carcinoma of the never-smokers/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

Omenn syndrome, a rare form of combined immunodeficiency in infants, presenting with recurrent infections, erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophilia, and increased serum IgE levels. It is a fatal condition unless treated by hematopoietic stem cell transplant. Hence, an early diagnosis and a prompt treatment can lead to better outcome in these unfortunate babies afflicted with Omenn syndrome. Here, we present an 8-week-old infant with typical features of Omenn syndrome, both clinically as well as on laboratory analysis, but surprising immunohistochemical findings on lymph node biopsy. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.

Langerhans cell histiocytosis is mainly diagnosed in children, and its manifestation in adult age is quite uncommon. Skin rashes may be non-specific and mimic a number of dermatoses. Therefore, the clinical diagnosis is challenging and as a rule, such patients are misinterpreted and managed for other disorders by a dermatologist for some years. We present a clinical case of Langerhans cell histiocytosis with skin involvement in a 35-year female patient, who had been treated by a dermatologist for 2 years for pyoderma, seborrheic dermatitis, and skin fold candidiasis. Taking into account the clinical signs and symptoms and age of manifestation, we initially suspected familial benign pemphigus (Hailey-Hailey disease) or follicular dyskeratosis (Darier's disease). However, the histological assessment showed Langerhans cell histiocytosis confirmed by immunohistochemistry with anti-langerin, anti-CD1a, and anti-protein S-100 antibodies. The patient was referred to a hematologist for further work-upand specific treatment. In cases of any treatment resistant disorders, which do not respond to long-term conventional treatment, it is necessary to reconsider the diagnosis by means of histological investigation. It would allow for identification of a disease, which is uncommon in dermatology practice.

Simple Summary: Human papillomavirus (HPV) has become the major risk factor for the development of oropharyngeal squamous cell carcinomas (OPSCCs), the incidence of which continues to grow in Western countries. Their biological features, associated with a better prognosis as well as a greater response to treatment, has already led to their staging system reclassification and to the development of clinical trials to deintensify the therapeutic approaches. In this context, we proposed to evaluate the recruitment levels of immune cells to ameliorate the classification of some groups of OPSCCs that are always associated with poor outcomes. For this purpose, we scored the density of CD8 and FoxP3 lymphocytes, CD68 macrophages and CD1a Langerhans cells and associated the significant cells with either p16 status or TNM staging to create strong combinations that demonstrated powerful prognostic values in such patients. These results encourage the development of further studies based on the inclusion of immune criteria in the classification of OPSCCs. The incidence of oropharyngeal cancers (OPSCCs) has continued to rise over the years, mainly due to human papillomavirus (HPV) infection. Although they were newly reclassified in the last TNM staging system, some groups still relapse and have poor prognoses. Based on their implication in oncogenesis, we investigated the density of cytotoxic and regulatory T cells, macrophages, and Langerhans cells in relation to p16 status, staging and survival of patients. Biopsies from 194 OPSCCs were analyzed for HPV by RT-qPCR and for p16 by immunohistochemistry, while CD8, FoxP3, CD68 and CD1a immunolabeling was performed in stromal (ST) and intratumoral (IT) compartments to establish optimal cutoff values for overall survival (OS). High levels of FoxP3 IT and CD1a ST positively correlated with OS and were observed in p16-positive and low-stage patients, respectively. Then, their associations with p16 and TNM were more efficient than the clinical parameters alone in describing patient survival. Using multivariate analyses, we demonstrated that the respective combination of FoxP3 or CD1a with p16 status or staging was an independent prognostic marker improving the outcome of OPSCC patients. These two combinations are significant prognostic signatures that may eventually be included in the staging stratification system to develop personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI), including monoclonal antibodies to programmed death 1, programmed death ligand 1, and cytotoxic T lymphocyte‐associated antigen 4, have provided great therapeutic benefits for cancer patients at advanced stages. However, the introduction of ICI frequently results in the development of immune‐related adverse events (irAE) through activation of autoreactive T cells. Here, we present three cases of cancer patients with cutaneous irAE, including development of de novo psoriasis and exacerbation of pre‐existing psoriasis. Interestingly, these patients shared an altered histological feature characterized by loss of epidermal CD1a+ cells, namely Langerhans cells (LC), in the psoriasiform lesions in contrast to "conventional psoriasis" exhibiting unchanged or activated LC. A possible underlying mechanism was that ICI‐mediated hyperactivation of effector T cells contributed to aggravation or establishment of psoriasis phenotype, which might be associated with direct cytotoxicity or expulsion of LC from the epidermis. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) incidence in Switzerland is rising due to factors like migration and globalization. The aim of this work was to investigate CL frequency in Switzerland and identify clinical and histopathological difficulties in diagnosing CL in a non-endemic country., Patients and Methods: This retrospective study evaluated the clinical and histopathological characteristics of all CL cases from two dermatopathology laboratories between 2000 and 2022. Skin biopsies were histopathologically reviewed using HE, Giemsa, and immunohistochemical stain for CD1a and a specific Leishmania antibody (LA). PCR to detect Leishmania DNA was performed if sufficient tissue was available., Results: 42 cases (27 m, 15 f) were included. The correct clinical diagnosis of CL was only made in 15 (35.7%) cases. In seven (16.6%) cases, CL was missed in the initial histopathologic evaluation. Two main histopathological patterns were observed: granulomatous and pseudolymphomatous. Immunohistochemical staining with CD1a and Leishmania-specific antibody was positive in 91% and 80% of cases, respectively. Leishmania PCR was positive in 25 of 26 cases, mainly detecting Old World species., Conclusions: CL is rare in Switzerland and often misdiagnosed clinically and histopathologically. CD1a and specific Leishmania antibody stainings are useful. CL should be considered in non-healing ulcers, even without a history of travel to endemic areas., (© 2024 Deutsche Dermatologische Gesellschaft (DDG).)

Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area.

Sinonasal polyps are benign projections of edematous nasal mucosa lined by respiratory epithelium. Langerhans cells (LCs) belonging to the dendritic cell family located in respiratory epithelium are involved in antigen presentation and maintenance of local immunological homeostasis. This study aims to elucidate the morphology and distribution of CD1a positive LCs in normal nasal mucosa and compare the same with polypoid nasal mucosa by immunohistochemistry. Normal nasal mucosa (n = 20) was obtained from patients who underwent septoplasty for deviated nasal septum. Polypoid nasal mucosa (n = 22) was obtained from patients with chronic rhinosinusitis (CRS) or allergic fungal rhinosinusitis who underwent excision of nasal polyps. The tissues obtained were processed for immunohistochemistry and stained with CD1a-EP80 Rabbit monoclonal antibody. In the tissues studied, CD1a positive LCs were observed in both the epithelium and lamina propria. Different morphological subtypes of LCs were noted in the epithelium. The cells were distributed adjacent to walls of subepithelial capillaries and cysts. The median number of CD1a positive LCs was significantly higher in polypoid category (13.5 per mm2) as compared with normal nasal mucosa (2.5per mm2) (p =.001). Presence of CD1a positive LCs in polypoid nasal mucosa hints at a critical immunological role in the etiopathogenesis of nasal polyps. [ABSTRACT FROM AUTHOR]

Simple Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and still orphan hematologic malignancy. No effective immunotherapeutic strategies are presently available for this poor prognosis disease. We here report the development and the preclinical evaluation of a novel bispecific T-cell engager (BTCE) that simultaneously targets CD1a and CD3ε (CD1a x CD3ε), therefore recruiting T cells against T-ALL cells. We demonstrate that this CD1a x CD3ε BTCE induces activation, proliferation, and cytokine release by T cells in co-cultures with CD1a expressing T-ALL cells, resulting in a concentration-dependent killing of leukemic cells in vitro. Moreover, CD1a x CD3ε BTCE inhibits the in vivo growth of human T-ALL xenografts and improves survival of immunocompromised mice reconstituted with human PBMC from healthy donors. We believe that this BTCE is suitable for clinical development for the treatment of CD1a-expressing T-ALL patients. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease. [ABSTRACT FROM AUTHOR]

Abstract Background The prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established. Methods We retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters. Results Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013). Conclusions Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment.

Rosai–Dorfman disease (RDD) is a nonneoplastic histiocytic proliferation. RDD is CD1a negative as opposed to Langerhans cell histiocytosis (LCH). The lesion was positive for CD1a immunohistochemistry in our RDD patient, suggesting an overlap with LCH. In addition, our case exhibited granulomatous angiitis (GA) on microscopy. We report the first triad of coexistent intracranial RDD-LCH-GA. A 30-year-old man presented with seizures, limb weakness, and violent behavior for 3 months. There was no fever, lymphadenopathy, or hepatosplenomegaly. Laboratory test results were normal. Radioimaging revealed an 8.6 cm × 7.4 cm × 3.2 cm mass in the parietotemporal lobe. It was hypointense on T1W1 and hypointense on T2W1, suggestive of glioma or tumefactive demyelination. A subtotal resection was performed. Histopathology exhibited mature lymphocytes, plasma cells, and histiocytes with emperipolesis. Vessels showed transmural granulomatous inflammation. Fungal and mycobacterial stains were negative. Immunohistochemistry revealed positivity for CD68, S100, and CD1a. The patient refused to undergo postoperative adjuvant radiotherapy. He remained asymptomatic for 6 months but was lost to follow-up thereafter. RDD-LCH concurrence may represent a clonal transformation in a common precursor histiocyte. Coexistent GA requires resection followed by steroid or cyclophosphamide therapy to prevent disease progression.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis caused by the expression of CD68-positive and CD1a-negative foam tissue cells, which is polar in pediatric patients. The study reports a case of an 8-year-old Chinese boy who presented with polydipsia and polyuria for 4 years, followed by central nervous system symptoms. Magnetic resonance imaging (MRI) showed a large lesion in the lateral ventricle. The histiocytes stained positively for CD68, CD163 and negatively for CD1a, glial fibrillary acidic protein (GFAP) and langerin, and were partially positive for S100 by immunohistochemical assay. More importantly, BRAFV 600E staining was positive in tissue, and the BRAF V600E mutations was also detected by real-time quantitative PCR (RT-qPCR) in the intracranial lesion tissue. According to our review of the literature, this is a rare case of ECD in the ventricle, with a younger age. [ABSTRACT FROM AUTHOR]

Keywords: CD1a; hair follicle; pseudolymphoma EN CD1a hair follicle pseudolymphoma 327 330 4 03/24/22 20220401 NES 220401 INTRODUCTION Pseudolymphomatous folliculitis (PLF) is a variant of cutaneous pseudolymphoma. Dermoscopy showed multiple follicular ostia and surface telangiectasia. gl HISTOPATHOLOGY Incisional skin biopsy revealed diffuse and dense lymphocytic infiltration from superficial to deep dermis. Histopathologically, PLF lesions show dense lymphocytic infiltrate throughout the entire dermis and may extend into the subcutaneous fat. [Extracted from the article]

Psoriasis is a chronic inflammatory skin disease characterized by Th17 responses. Recent evidence has identified Langerhans cells to have a key role in disease pathogenesis, with constitutive high expression of CD1a and capacity to present lipid antigens to T cells. Phospholipase A2 enzymes generate neolipid antigens for recognition by CD1a‐reactive T cells; however, the broader enzymatic pathways of CD1a lipid ligand generation have not been thoroughly investigated. In this study, we used immunofluorescence of skin and ELISpot analyses of CD1a‐reactive T cells to investigate the role of the lipase acyloxyacyl hydrolase (AOAH) in CD1a ligand generation with relevance to the pathogenesis of psoriasis. We found that the PLA2 activity of rAOAH leads to the activation of circulating CD1a auto‐reactive T cells, leading to the production of IFN‐γ and IL‐22. Circulating AOAH‐responsive CD1a‐reactive T cells from patients with psoriasis showed elevated IL‐22 production. We observed that AOAH is highly expressed in psoriatic lesions compared to healthy skin. Overall, these data present a role for AOAH in generating antigens that activate circulating lipid‐specific CD1a‐restricted T cells and, thus, contribute to psoriatic inflammation. These findings suggest that inhibition of PLA2 activity of AOAH may have therapeutic potential for individuals with psoriasis. [ABSTRACT FROM AUTHOR]

Objective: To explore the role of dendritic cells in the pathogenesis of leprosy. Method: The expression of three dendritic cell markers (CD123, FXⅢA, CD1a) in leprosy lesions was assessed by immunohistochemical staining, and their significance was analyzed. Results: Expression of CD123, FXⅢA and CD1a was observed in tuberculoid granulomas of paucibacillary leprosy lesion, while lesion of multibacillary leprosy displayed no or minimal expression. Conclusions: CD123, FXⅢA and CD1a positive dendritic cells participate in the cellular immune response in leprosy, and promote the development of the disease toward paucibacillary type.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis caused by the expression of CD68-positive and CD1a-negative foam tissue cells, which is polar in pediatric patients. The study reports a case of an 8-year-old Chinese boy who presented with polydipsia and polyuria for 4 years, followed by central nervous system symptoms. Magnetic resonance imaging (MRI) showed a large lesion in the lateral ventricle. The histiocytes stained positively for CD68, CD163 and negatively for CD1a, glial fibrillary acidic protein (GFAP) and langerin, and were partially positive for S100 by immunohistochemical assay. More importantly, BRAFV600E staining was positive in tissue, and the BRAFV600E mutations was also detected by real-time quantitative PCR (RT-qPCR) in the intracranial lesion tissue. According to our review of the literature, this is a rare case of ECD in the ventricle, with a younger age.

Background: Langerhans cell histiocytosis (LCH) is a rare malignant disorder of epidermal antigen presenting cells. It is characterized by infiltration of various tissues with dendritic cells (Langerhans cells, LC) that express CD1a or CD207 (langerin), often leading to organ dysfunction. A patient with LCH required liver transplantation (LT) for LCH-associated biliary-tract disease. Cholangiopathy developed after LT. The question arose: In this patient, did LC in damaged liver-allograft biliary epithelium signify acute cellular rejection (ACR) or recurrent LCH?, Methods: We evaluated immunohistochemical identification of LC (CD1a, CD207) in the proposita and in 14 ACR patient samples as distinguishing between ACR and recurrent LCH., Results: Among 15 patient samples, 3 (20%) marked with neither antibody. Among the remaining 12 samples (80%), 4 (26.7%)-including that from the proposita-had cells marking for both antigens within bile-duct epithelium as well as in surrounding portal-tract connective tissue, 2 (13.3%) had cells marking for both antigens in one region or the other, but not in both, and 6 (40%) had cells marking for only one antigen in one region or the other., Conclusions: Immunostaining for CD1a and CD207/langerin in the setting of ACR without suspicion of LCH identifies LC in damaged bile ducts. This biomarker pairing proved not to be LCH-specific. Our findings indicate that the presence of these cells alone is insufficient to identify recurrent LCH in the allograft liver., (© 2024 The Author(s). Pediatric Transplantation published by Wiley Periodicals LLC.)

Objective: The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients. Methods: PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ2 test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS. Results: 25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (r = 0.30409, p < 0.001) and CD83 levels (r = 0.6146, p < 0.001) in breast carcinoma tissue, as well as CD83 levels (r = 0.17508, p = 0.027) in lymph node. The median OS was 83 months (range 12–106), and the 3- and 5-year OS rates were 94.97% (95% CI 91.57–98.37) and 86.79% (95% CI 81.53–92.06), respectively. Moreover, patients with high median CD1a levels had a significantly lower 5-year OS rate (75.6%) than those with low median CD1a levels (93.5%, p = 0.038). Conclusion: PD-L1, CD1a, and CD83 are variably expressed in triple-negative breast carcinoma tissues, and PD-L1 expression correlates with CD1a and CD83. Higher CD1a levels correlate with PD-L1 expression and predict worse OS in triple-negative breast carcinoma. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis lesions are characterized by CD1a+ myeloid lineage LCH cells and an inflammatory infiltrate of cytokines and immune cells, including T cells. T cells that recognize CD1a may be implicated in the pathology of many disease states including cancer and autoimmunity but have not been studied in the context of LCH despite the expression of CD1a by LCH cells. In this perspective article, we discuss the expression of CD1a by LCH cells, and we explore the potential for T cells that recognize CD1a to be involved in LCH pathogenesis. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis lesions are characterized by CD1a+ myeloid lineage LCH cells and an inflammatory infiltrate of cytokines and immune cells, including T cells. T cells that recognize CD1a may be implicated in the pathology of many disease states including cancer and autoimmunity but have not been studied in the context of LCH despite the expression of CD1a by LCH cells. In this perspective article, we discuss the expression of CD1a by LCH cells, and we explore the potential for T cells that recognize CD1a to be involved in LCH pathogenesis.

Background: Langerhans cells (LCs) are antigen‐presenting cells that are characterized by CD1a and CD207/langerin expression. The disturbance in the communication network among keratinocytes, melanocytes, and antigen‐presenting cells may be involved in vitiligo pathogenesis. Aims: The current work aims to detect and quantify LCs in involved skin of patients affected by vitiligo before and after treatment with NB‐UVB using CD1a immunohistochemistry, in addition to correlate percentage of LCs with the clinicopathological parameters. Methods: Twenty vitiligo patients and 10 age and sex matched controls were investigated. Patients were received NB‐UVB thrice weekly for 12 weeks. Results: There was a significant reduction in LCs percentage in skin affected by vitiligo before treatment in comparison with normal skin. About 65% (13/20) of vitiligo patients responded to NB‐UVB, and the liability to respond was correlated with LCs percentage in specimens before treatment. However, there was no statistical difference between specimens before and after treatment regarding LCs percentage. Conclusions: Reduction in LCs in vitiligo may be a sign of active disease and melanocytes destruction. The percentage of LCs affects response to NB‐UVB since higher percentage is associated with greater response to therapy. Therefore, modulation of LCs as a type of immunotherapy could be beneficial in improvement of vitiligo. [ABSTRACT FROM AUTHOR]

Background: The prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established.Methods: We retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters.Results: Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013).Conclusions: Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment. [ABSTRACT FROM AUTHOR]

The association among Langerhans cell histiocytosis, hematolymphoid malignancies, and heavy smoking has been addressed in medical literature to identify a possible potential link. Such occurrence can pose diagnostic challenges, as well as important clinical implications for disease progression and treatment approaches. We present pulmonary Langerhans cell histiocytosis instance in a 35-year-old male patient, with a 34-pack-year smoking history and nodular sclerosing Hodgkin lymphoma stage IIB who developed multiple bilateral lung nodules. The patient completed 6 cycles of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine chemotherapy and radiotherapy 2 years earlier. CT chest scans revealed numerous micronodules scattered randomly throughout the upper and lower left lung lobes. Subsequent wedge resection exhibited cellular proliferation with grooved nuclei, eosinophilic cytoplasm, and surrounding inflammatory components. Immunohistochemical staining showed positive staining for S100 and CD1a confirming a diagnosis of pulmonary Langerhans cell histiocytosis. The patient responded to a 6-week treatment with vinblastine and prednisolone. A subsequent CT scan of the lungs revealed complete resolution after 3 years. This report underscores the importance of identifying pulmonary Langerhans cell histiocytosis in heavy smokers with Hodgkin lymphoma presenting with multiple nodular pulmonary lesions. For patients with Hodgkin lymphoma and a possible genetic predisposition, smoking may contribute to the overt development of pulmonary Langerhans cell histiocytosis. Therefore, smoking cessation and careful follow-up examinations are required. Further research is recommended to elucidate the underlying mechanisms of this intriguing association. [ABSTRACT FROM AUTHOR]

Cluster of differentiation 1 (CD1) is a family of cell-surface glycoproteins that present lipid antigens to T cells. Humans have five CD1 isoforms. CD1a is distinguished by the small volume of its antigen-binding groove and its stunted A′ pocket, its high and exclusive expression on Langerhans cells, and its localization in the early endosomal and recycling intracellular trafficking compartments. Its ligands originate from self or foreign sources. There are three modes by which the T-cell receptors of CD1a-restricted T cells interact with the CD1a:lipid complex: they bind to both the CD1a surface and the antigen or to only CD1a itself, which activates the T cell, or they are unable to bind because of bulky motifs protruding from the antigen-binding groove, which might inhibit autoreactive T-cell activation. Recently, several studies have shown that by producing TH2 or TH17 cytokines, CD1arestricted T cells contribute to inflammatory skin disorders, including atopic dermatitis, psoriasis, allergic contact dermatitis, and wasp/bee venom allergy. They may also participate in other diseases, including pulmonary disorders and cancer, because CD1a-expressing dendritic cells are also located in non-skin tissues. In this mini-review, we discuss the current knowledge regarding the biology of CD1a-reactive T cells and their potential roles in disease. [ABSTRACT FROM AUTHOR]

• CD1-restricted T cells including Invariant Natural Killer cells (iNKT) are innate lymphocytes with potent cytotoxic and cytokine effector functions. • Highly-specific methods have been developed for therapeutic targeting of iNKT cells in cancers, inflammatory, infectious and autoimmune diseases. • Uniform safety, evidence of immunologic activity and increasingly clinical efficacy have been seen. • Approaches to targeting iNKT cells in clinical development include natural glycolipid ligands, chemical analogues thereof and monoclonal antibody-based targeting. • Approaches to targeting iNKT cells in clinical development include natural glycolipid ligands, chemical analogues thereof and monoclonal antibody-based targeting. CD1-restricted T cells were first described over 30 years ago along with the cloning of the CD1 family. Around the same time, invariant Natural Killer cells (iNKT) were identified based on invariant TCR-alpha chains with additional expression of natural killer (NK) cell markers. About 5 years later, iNKT were shown to react with CD1d. Since then, iNKT have been shown to be a major population of CD1d-restricted T cells in humans and many animals. Like NK cells, iNKT are innate lymphocytes with rapid and wide-ranging effector potential. These activities include cytotoxicity and an unusually broad and high-level cytokine production. The development of highly-specific methods of isolating, stimulating, expanding or depleting these relatively rare cells and controlling their potent activities has stimulated considerable interest in therapeutic targeting of iNKT cells. Potential applications include cancers, inflammatory, infectious and autoimmune among other diseases. To date, most trials have targeted various cancers, there are 2 published trials in viral hepatitis and one in sickle cell lung disease. Uniform safety, evidence of immunologic activity and increasingly clinical efficacy have been seen. Approaches to targeting iNKT cells in clinical development include highly specific natural glycolipid ligands presented by CD1d and chemical analogues thereof and monoclonal antibody-based targeting of iNKT cells. In the case of iNKT cell-based therapies, novel approaches include arming them with Chimeric Antigen Receptors (CARs) and recombinant TCRs (rTCR), gene editing and allogeneic use. Controlling the iTCR:CD1d molecular interaction and consequences is a unique and promising therapeutic technology. [ABSTRACT FROM AUTHOR]

Pseudolymphomatous folliculitis (PLF) is a subtype of cutaneous pseudolymphoma that is recognized as an independent disease. PLF is characterized by dermal lymphocytic infiltration surrounding an irregular hyperplastic pilosebaceous unit (i.e., activated pilosebaceous unit). An interstitial distribution of CD1a‐positive cells is regarded as an important feature of PLF, especially in distinguishing it from primary cutaneous marginal zone lymphoma (PCMZL), which is associated with a peripheral concentration of CD1a‐positive cells. We undertook a clinicopathological investigation of PLF, with a reassessment of CD1a immunohistochemistry. We defined diagnostic criteria for PLF based on past studies and consequently identified 79 cases. In addition, we collected 32 cases of PCMZL and performed detailed clinical, pathological, and immunohistochemical investigations using antibodies to CD3, CD20, and CD1a. We found an interstitial concentration of CD1a‐positive cells in 90.2% of PLF and 34.5% of PCMZL cases. The peripheral concentration of CD1a‐positive cells was seen in 9.8% of PLF and 34.5% of PCMZL cases. In both diseases, CD1a‐positive cells appeared in T‐cell nests (88.5% in PLF and 92.9% in PCMZL) but were absent in B‐cell nests (0% in both groups). All 79 cases of PLF showed activated pilosebaceous units while 22 of the 32 PCMZL cases displayed pilosebaceous units, although none of these were activated. In summary, regarding the distribution patterns of CD1a‐positive cells as a diagnostic feature in distinguishing between PLF and PCMZL is somewhat inconclusive. To differentiate PLF and PCMZL, determining the presence or absence of activated pilosebaceous units is essential. [ABSTRACT FROM AUTHOR]

The current study aimed to determine the histopathological and immunohistochemical effects of two types of tattoo inks (Decorative and cosmetic) imported from original and brand companies that supply the tattoo centers with inks on the skin of Syrian hamsters. An adult 120 Syrian hamsters (40 males, and 80 females) were randomly divided into 24 groups. Male groups included (2 groups as controls, 3 groups tattooed with original brands decorative inks, and 3 groups tattooed with fake brands decorative inks. While, female groups involved (4 groups as controls, 3groups tattooed with the original brand decorative inks, 3 groups tattooed with the fake brand decorative inks, 3 groups tattooed with the original brand cosmetic inks, and 3 groups tattooed with the fake brand cosmetic inks). After 60 days, animals were sacrificed and the skin samples were isolated and fixated for histopathological and Immunohistochemical studies. Skin sections showed congestion and cellular infiltration in the dermal layer, atrophy of the subcutaneous layer, follicular cells, loss of stratum corneum in some injected skin, and increased thickness of stratum corneum of tattooed groups. Other manifests involved different degrees of necrosis in epidermal and subcutaneous layers, and increase and decrease hair follicles in the skin of some tattooed hamsters comparing with control groups. Additionally, skin tissue showed hypertrophy in the stratum spinosum and hyperplasia of follicular cells in some tattooed animals. Moreover, ink injection caused sloughing and involution in the connective tissue of the dermal and epidermal layers, hypertrophy and hyperplasia of fibroblasts in most tattooed groups. Lastly, skin sections of some tattooed hamsters exhibited, acanthosis and granulomatosis. Whereas, immunohistochemical staining showed that the infiltrates in the dermal layer contained especially Langerhans and lymphocytes. Whereas most groups of tattooed hamsters appeared various scores of CD1a, CD3 and CD20 staining that ranged from weak to intense. The CD1a antibody appeared mostly moderate positive staining in most tattooed hamsters. While, CD3 antibody exhibited weak, mild and severe staining in both the males and females groups tattooed with the original brand decorative inks and weak to moderate in both males and females groups injected with the fake brand decorative inks. The cosmetic groups showed weak to moderate staining of the CD3 marker. Lastly, the CD20 antibody stained most skin sections of tattooed animals and the staining was mostly weak and mild in few groups. [ABSTRACT FROM AUTHOR]