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Simple Summary: Lung cancer is the most lethal cancer worldwide. Recently, immunotherapy has revolutionized the therapeutic landscape of pulmonary non-small cell carcinomas. While the utilization of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis has improved survival, only a small percentage of cases will show a durable response. In this project, we aim to assess the potential of CXCL13+ cells to identify good responders to immunotherapy. Our results showed that the density and the localization of these cells are associated with the extent of the response to immune checkpoint inhibitors in advanced non-small cell lung cancers. This research provides new insights into the roles of the tumor microenvironment in modulating response to immunotherapy. Background: Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancers (NSCLCs) treatment, but only 20–30% of patients benefit from these treatments. Currently, PD-L1 expression in tumor cells is the only clinically approved predictor of ICI response in lung cancer, but concerns arise due to its low negative and positive predictive value. Recent studies suggest that CXCL13+ T cells in the tumor microenvironment (TME) may be a good predictor of response. We aimed to assess if CXCL13+ cell localization within the TME can predict ICI response in advanced NSCLC patients. Methods: This retrospective study included 65 advanced NSCLC patients treated with Nivolumab/Pembrolizumab at IUCPQ or CHUM and for whom a pretreatment surgical specimen was available. Good responders were defined as having a complete radiologic response at 1 year, and bad responders were defined as showing cancer progression at 1 year. IHC staining for CXCL13 was carried out on a representative slide from a resection specimen, and CXCL13+ cell density was evaluated in tumor (T), invasive margin (IM), non-tumor (NT), and tertiary lymphoid structure (TLS) compartments. Cox models were used to analyze progression-free survival (PFS) and overall survival (OS) probability, while the Mann–Whitney test was used to compare CXCL13+ cell density between responders and non-responders. Results: We showed that CXCL13+ cell density localization within the TME is associated with ICI efficacy. An increased density of CXCL13+ cells across all compartments was associated with a poorer prognostic (OS; HR = 1.22; 95%CI = 1.04–1.42; p = 0.01, PFS; HR = 1.16; p = 0.02), or a better prognostic when colocalized within TLSs (PFS; HR = 0.84, p = 0.03). Conclusion: Our results support the role of CXCL13+ cells in advanced NSCLC patients, with favorable prognosis when localized within TLSs and unfavorable prognosis when present elsewhere. The concomitant proximity of CXCL13+ and CD20+ cells within TLSs may favor antigen presentation to T cells, thus enhancing the effect of PD-1/PD-L1 axis inhibition. Further validation is warranted to confirm the potential relevance of this biomarker in a clinical setting. [ABSTRACT FROM AUTHOR]

• Mast cells (MCs), a type of innate immune cells, come from myeloid stem cells. MCs show different roles in cancer. • MCs have pro-tumorigenic or anti-tumorigenic role depending on the type of cancer, the degree of tumor progression, and the location of these immune cells in the tumor bulk. • Regulation of MC activation, recruitment, and type of released mediators at the tumor site can be useful for management and control of tumor growth. Please find the new points, You can replace these points with the previous version. Mast cells (MCs), a type of innate immune cells, are derived from myeloid stem cells, sometimes known as mastocytes or labrocytes, and contain many granules rich in histamine and heparin. The mentioned cells are able to release various mediators such as cytokines, leukotrienes, and a large number of proteases into the environment. Many studies and experiments have established the infiltration of MCs into the tumor site. However, the findings are highly controversial to determine whether these immune cells contribute to the growth and development of the tumor or cause anti-tumor immune responses. Various studies have revealed that MCs have a pro-tumorigenic or anti-tumorigenic role depending on the type of cancer, the degree of tumor progression, and the location of these immune cells in the tumor bulk. Although these types of immune cells cause angiogenesis and tumor progression in some cancers, they have a significant anti-tumor role in some other types of cancers. In general, although a number of studies have specified the protective role of MCs in cancers, the increased number of MCs in the blood and microenvironment of tumors, as well as the increased level of angiogenesis and tumor progression, has been indicated in another array of studies. The function of MCs against or in favor of the cancers still requires further investigations to more accurately and specifically determine the role of MCs in the cancers. The function of MCs in tumors and their various roles in case of exposure to the cancer cells have been addressed in the present review. The concluding section of the present study recommends a number of methods for modification of MCs in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) can control cancer and cancer stem cells (CSCs), and this topic has drawn immense attention recently. Stem cells are a tiny population of a bulk of tumor cells that have enormous potential in expansion and metastasis of the tumor. miRNA have a crucial role in the management of the function of stem cells. This role is to either promote or suppress the tumor. In this review, we investigated the function and different characteristics of CSCs and function of the miRNAs that are related to them. We also demonstrated the role and efficacy of these miRNAs in breast cancer and breast cancer stem cells (BCSC). Eventually, we revealed the metastasis, tumor formation, and their role in the apoptosis process. Also, the therapeutic potential of miRNA as an effective method for the treatment of BCSC was described. Extensive research is required to investigate the employment or suppression of these miRNAs for therapeutics approached in different cancers in the future. In the present review, we characterized the function and different characteristics of breast cancer stem cells and the function of microRNAs that are related to them. [ABSTRACT FROM AUTHOR]

Highlights • Cancer stem cells (CSCs) have the ability to self-regenerate and recurrent the tumor. • The immune system can somehow fight with CSCs, but will eventually become weakened by these cancerous cells. • The immune cells are altered when they come into contact with CSCs, and somewhat obedient to the tumor. Abstract Cancer stem cells (CSCs) are a subgroup of tumor cells that are characterized by their tumor initiating capacity, low proliferation rate, self-renewal capacity, pluripotency and chemoresistance. The immune system, including innate and adaptive immune cells, plays pro-tumorigenic and anti-tumorigenic roles in cancer biology. Immunosurveillance often initially successfully eradicates tumor cells. However, following a phenomenon referred to as immunoediting, cancer cells may ultimately evade immune destruction, thus enabling tumor progression. Here, we review how CSCs both escape immune destruction and foster establishment of an immunosuppressive tumor microenvironment through intricate interactions with and recruitment of a broad range of immune cells, including natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), tumor-associated macrophages (TAMs), cytotoxic T-lymphocytes (CTLs) and T helper (Th) cells. Further elucidation of CSC-immune cell interactions and the underlying signaling mechanisms will open up novel opportunities to improve cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells seem to be the most common innate lymphocyte subtypes, and they're known for their ability to guide anti-tumor and anti-viral responses, making them potentially therapeutic. Since NK cells lack polymorphic clonotypic receptors, they must rely on inhibitory receptors to develop, mature, and distinguish between "self" and "non-self." In the clinic, genetically engineered immune cells expressing a chimeric antigen receptor (CAR) that consists of an extracellular antigen recognizing domain connected to an intracellular signaling domain have gained interest. The U.S. food and drug administration (FDA) approved two CAR-T cells, anti-CD19 CARs, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). Nevertheless, CAR-T cell therapy is linked to a series of negative side effects, including fatal cytokine release syndrome (CRS) and tumor lysis syndrome (TLS), as well as a lack of regulatory control. CAR-transduced NK cells (CAR-NK) are thought to have many benefits, including clinical safety, the mechanisms by which they identify cancerous cells, and their abundance in clinical specimens, according to a growing number of studies. In pre-clinical and clinical trials, human primary NK cells and the NK-92 cell line were effectively transduced to express CARs against hematological cancers and solid tumors. Here, it is tried to summarize the development of CAR-NK cells, challenges and coping strategies, as well as managing the challenges and obstacles related to its protection, which promises to eliminate the shortcomings of conventional CARs. • Immune cells expressing a chimeric antigen receptor (CAR) connected to an intracellular signaling domain have gained interest. • CAR-transduced NK cells (CAR-NK) are thought to have many benefits, including clinical safety, the mechanisms by which they identify cancerous cells. • The practical implementation of CAR-NK cell treatments is linked to significant challenges that must be overcome for them to realize their greatest capacity. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2)‐positive breast cancer (BC) comprises around 20–30% of all BC subtypes and is correlated with poor prognosis. For many years, trastuzumab, a monoclonal antibody, has been used to inhibit the HER2 activity. Though, the main resistance to trastuzumab has challenged the use of this drug in the management of HER2‐positive BC. Therefore, the determination of resistance mechanisms and the incorporation of new agents may lead to the development of a better blockade of the HER family receptor signaling. During the last few years, some therapeutic drugs have been developed for treating patients with trastuzumab‐resistant HER2‐positive BC that have more effective influences in the management of this condition. In this regard, the present study aimed at reviewing the mechanisms of trastuzumab resistance and the innovative therapies that have been investigated in trastuzumab‐resistant HER2‐positive BC subjects. [ABSTRACT FROM AUTHOR]

Purpose: The cytotoxic properties upon treatment with nicotine have been reported in several studies, but the underlying mechanisms remain not fully defined. The alpha7 nicotinic acetylcholine receptor (α7nAChR) is one of the important nicotinic receptors, which nicotine partly by binding to this receptor exerts its effects. The current study aimed to investigates the influences of nicotine on cellular proliferative and apoptotic activities and tried to determine the involvement of α7nAChR in these functions. Methods: Human hepatocellular carcinoma (HepG2) cell line was used to determine the individual or combined effects of treatments with nicotine (10 μM) and specific siRNA (100 nM) targeting α7nAChR expression. The MTT assay, DAPI staining assay, and flow cytometry assay were applied to measure the cell viability, apoptosis and cell cycle progression of the cells, respectively. In addition, the changes in the mRNA level of the genes were assessed by qRT-PCR. Results: Compared to control groups, the cells treated with nicotine exhibited significant dose-dependent decreases in cell viability (log IC50 = -5.12 ± 0.15). Furthermore, nicotine induced apoptosis and cell cycle arrest especially at G2/M Phase. The qRT-PCR revealed that nicotine increased the mRNA levels of α7nAChR as well as caspase-3 and suppressed the expression of cyclin B1. Treatment with α7-siRNA abolished these effects of nicotine. Conclusion: These experiments determined that upregulation of α7nAChR by nicotine inhibits HepG2 cells proliferation and induces their apoptosis. These effects blocked by treatment with α7-siRNA, which indicates the involvement of α7nAChR pathways in these processes. [ABSTRACT FROM AUTHOR]

Nasal polyps (NP) are associated with inflamed mucosa of unknown etiology. The role of T cells in nasal polyposis is unclear. Invariant natural killer T cells (iNKT) can promote Th2 responses and have been implicated in some types of asthma. As there are shared inflammatory pathways involved in asthma and NPs, we evaluated the frequency of iNKT in 17 patients with NPs, but without asthma. A median of 6% polyp cells were T lymphocytes, of which iNKT were 0 to 2.38% (mean 0.674%). In the matched group (n = 10), iNKT in NPs was significantly higher than PBMCs (1.057% vs 0.155%, P < 0.05). Relative expression of Vα24 to TCR-beta genes in polyps (n = 14) was higher than blood in matched samples (n = 4). The presence of greater proportions of iNKT in NPs than in blood suggests that iNKT may play a role in the pathogenesis of nasal polyposis. [ABSTRACT FROM AUTHOR]

Glioblastoma, also known as glioblastoma multiforme, is the most aggressive brain tumor in adults. Despite the huge advance in developing novel therapeutic strategies for patients with glioblastoma, the appearance of multidrug resistance (MDR) against the common chemotherapeutic agents, including temozolomide, is considered as one of the important causes for the failure of glioblastoma treatment. On the other hand, recent studies have demonstrated the critical roles of long non-coding RNAs (lncRNAs), particularly in the development of MDR in glioblastoma. Therefore, this article aimed to review lncRNA's contribution to the regulation of MDR and elucidate the underlying mechanisms in glioblastoma, which will open up new lines of inquiry in the treatment of glioblastoma. [ABSTRACT FROM AUTHOR]