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Tumor-infiltrating lymphocytes are considered clinically beneficial in breast cancer, but the significance of natural killer (NK) cells is less well characterized. As increasing evidence has demonstrated that the spatial organization of immune cells in tumor microenvironments is a significant parameter for impacting disease progression as well as therapeutic responses, an improved understanding of tumor-infiltrating NK cells and their location within tumor contextures is needed to improve the design of effective NK cell-based therapies. In this study, we developed a multiplex immunohistochemistry (mIHC) antibody panel designed to quantitatively interrogate leukocyte lineages, focusing on NK cells and their phenotypes, in two independent breast cancer patient cohorts (n = 26 and n = 30). Owing to the clinical evidence supporting a significant role for NK cells in HER2 + breast cancer in mediating responses to Trastuzumab, we further evaluated HER2 - and HER2 + specimens separately. Consistent with literature, we found that CD3 + T cells were the dominant leukocyte subset across breast cancer specimens. In comparison, NK cells, identified by CD56 or NKp46 expression, were scarce in all specimens with low granzyme B expression indicating reduced cytotoxic functionality. Whereas NK cell density and phenotype did not appear to be influenced by HER2 status, spatial analysis revealed distinct NK cells phenotypes regarding their proximity to neoplastic tumor cells that associated with HER2 status. Spatial cellular neighborhood analysis revealed multiple unique neighborhood compositions surrounding NK cells, where NK cells from HER2 - tumors were more frequently found proximal to neoplastic tumor cells, whereas NK cells from HER2 + tumors were instead more frequently found proximal to CD3 + T cells. This study establishes the utility of quantitative mIHC to evaluate NK cells at the single-cell spatial proteomics level and illustrates how spatial characteristics of NK cell neighborhoods vary within the context of HER2 - and HER2 + breast cancers., Competing Interests: Declarations. Ethics approval: Cohort 1 samples were obtained from Duke University, Durham, USA. Informed consent was obtained from all human subjects included in this study. The study protocol was approved by the ethics committee IRB of Duke University (Pro00034242). Cohort 2 samples were obtained by Maastricht University Medical Center+, Maastricht, The Netherlands. The collection, storage, and use of tissue and patient data were performed in agreement with the “Code for Proper Secondary Use of Human Tissue in the Netherlands” and approved by the local ethics committee (METC 2019 − 1154). Consent for publication: Not applicable. Conflict of interest: C.B. Betts is an employee of, and holds equity in, Akoya Biosciences, Inc. L.M. Coussens has received reagent support from Cell Signaling Technologies, Syndax Pharmaceuticals, Inc., ZielBio, Inc., and Hibercell, Inc.; holds sponsored research agreements with Syndax Pharmaceuticals, Hibercell, Inc., Prospect Creek Foundation, Lustgarten Foundation for Pancreatic Cancer Research, Susan G. Komen Foundation and the National Foundation for Cancer Research; is on the Advisory Board for Carisma Therapeutics, Inc., CytomX Therapeutics, Inc., Kineta, Inc., Hibercell, Inc., Cell Signaling Technologies, Inc., Alkermes, Inc., Raska Pharma, Inc., NextCure, Guardian Bio, AstraZeneca Partner of Choice Network (OHSU Site Leader), Genenta Sciences, Pio Therapeutics Pty Ltd., and Lustgarten Foundation for Pancreatic Cancer Research Therapeutics Working Group, Inc., (© 2025. The Author(s).)

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Lymphocytes are the primary executors of the immune system and play essential roles in tumorigenesis and development. We investigated the dynamic changes in peripheral blood lymphocyte subsets to predict the efficacy of chemotherapy or combination immunotherapy in NSCLC., Methods: This retrospective study collected data from 81 patients with NSCLC who received treatments at the First Affiliated Hospital of Zhengzhou University from May 2021 to May 2023. Patients were divided into response and non-response groups, chemotherapy and combination immunotherapy groups, and first-line and multiline groups. We analyzed the absolute counts of each lymphocyte subset in the peripheral blood at baseline and after each treatment cycle. Within-group and between-group differences were analyzed using paired Wilcoxon signed-rank and Mann-Whitney U tests, respectively. The ability of lymphocyte subsets to predict treatment efficacy was analyzed using receiver operating characteristic curve and logistic regression., Results: The absolute counts of lymphocyte subsets in the response group significantly increased after the first cycle of chemotherapy or combination immunotherapy, whereas those in the non-response group showed persistent decreases. Ratios of lymphocyte subsets after the first treatment cycle to those at baseline were able to predict treatment efficacy early. Combination immunotherapy could increase lymphocyte counts compared to chemotherapy alone. In addition, patients with NSCLC receiving chemotherapy or combination immunotherapy for the first time mainly presented with elevated lymphocyte levels, whereas multiline patients showed continuous reductions., Conclusion: Dynamic surveillance of lymphocyte subsets could reflect a more actual immune status and predict efficacy early. Combination immunotherapy protected lymphocyte levels from rapid decrease and patients undergoing multiline treatments were more prone to lymphopenia than those receiving first-line treatment. This study provides a reference for the early prediction of the efficacy of clinical tumor treatment for timely combination of immunotherapy or the improvement of immune status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LZ declared a shared parent affiliation with the authors, and the reviewer XR declared a past co-authorship with the author YZ at the time of the review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhen, Wang, Qin, Lu, Yang and Zhang.)

Background: Although peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear., Methods: We prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features., Results: We found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05)., Conclusion: Circulating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Huang, Liu, Chen, Li, He, Peng, Liang, Li and Liu.)

We aimed to investigate the correlation between lymphocyte subpopulations expressing inhibitor receptors, IL-6 levels, and the efficacy of immunotherapy in patients with hepatocellular carcinoma. Blood samples were prospectively collected before and after immunotherapy from patients with intermediate and advanced hepatocellular carcinoma who were treated with immunotherapy at the Fifth Medical Center of the PLA General Hospital from August 2022 to October 2023. According to the efficacy of the patients, patients were divided into effective and ineffective groups, with 40 in the effective group and 44 in the ineffective group. We compared changes in lymphocyte subsets and IL-6 levels between the two groups. Optimal cut-off value was determined using ROC curves. Then, patients were categorized into high and low groups based on cut-off value, and the disease control rates and progression free survival were compared. Before immunotherapy, there were no significant differences in the baseline levels of lymphocyte subsets (PD1 + TIM3 + T/T, TIGIT + T/T, TIM3 + T/T, CTLA4 + T/T, LAG3 + T/T, PD1 + T/T) and IL-6 between the two groups (P > 0.05). After immunotherapy, the levels of PD1 + TIM3 + T/T, TIGIT + T/T, and IL-6 in the effective group were lower than those in the ineffective group and these differences were statistically significant (P = 0.001, P = 0.008, P = 0.000). However, the levels of other lymphocyte subsets showed no significant difference. Using the ROC curve to assess efficacy prediction, PD1 + TIM3 + T/T, TIGIT + T/T and IL-6 demonstrated high predictive ability (AUC = 0.79, AUC = 0.81, AUC = 0.78). The predictive value of efficacy was further improved when all three factors were combined (AUC = 0.92, P = 0.000). Based on the ROC curve, we identified optimal cut-off value for three factors. Notably, patients with values below the optimal cut-off value had higher disease control rate and progression free survival. The levels of PD1 + TIM3 + T/T, TIGIT + T/T, and IL-6 after 2 cycles of immunotherapy may serve as predictors of treatment efficacy in patients with hepatocellular carcinoma., (© 2023. The Author(s).)

Background: Neutrophil/lymphocyte ratio (NLR) is a vital index for systemic inflammation and a prognostic indicator for gastric cancer (GC). Despite the abundant literature on NLR's prognostic value for GC, the underlying factors mediating its impact on survival remain unclear. The objective of this study was to analyze the role of NLR in different prognostic models and subgroups, and investigate the mediating effects of immune infiltrates between NLR and survival., Methods: A total of 924 patients who underwent D2 lymph node resection were enrolled in this study. According to the level of NLR, patients were divided into two groups, the high and low NLR groups. Clinical parameters, indexes related to immune infiltrates, and survival were compared between the two groups. Prognostic models, interaction analysis, and mediating effects analysis were performed to investigate the clinical association of NLR, immune infiltrates, and survival., Results: The infiltration of CD3+ and CD8+ T cells was significantly different in the two NLR groups. The level of NLR was an independent prognostic predictor of GC. In addition, an interaction effect exists between NLR and MMR status on the prognosis of GC (p-interaction <0.01). Lastly, the mediating effect analysis revealed that the infiltration level of CD3+ T cells was the mediating factor between NLR and survival (p < 0.001)., Conclusions: The level of NLR is an independent prognostic predictor of GC. The effect of NLR on prognosis is partly mediated by CD3+ T-cell infiltration., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Lymphocytes play crucial roles in tumor surveillance in diffuse large B-cell lymphoma (DLBCL). Neutrophil-to-lymphocyte ratio (NLR), a biomarker for systematic inflammation, has been confirmed to be a prognostic factor for many malignant diseases. Herein, we conducted a systemic in-depth study of circulating neutrophils and lymphocyte subsets in DLBCL patients and their dynamics along with chemoimmunotherapy. A total of 61 patients with DLBCL were enrolled. Detection of lymphocyte subsets by flow cytometry was conducted at diagnosis and after 2/4/6/8 cycles' treatment of R-CHOP. Clinical significance, including incidence of infection, curative effect and disease-free survival (DFS), was analyzed based on the patients' clinical data and the quantity of lymphocyte subsets. The absolute numbers of neutrophils in stage III-IV DLBCL patients were obviously increased (p = 0.012), while the absolute numbers of lymphocytes were decreased (p = 0.025). Consequently, DLBCL patients had significantly higher NLR than healthy controls (p < 0.001). Further analysis of lymphocyte subsets showed a significantly reduced CD4 + T cells in DLBCL patients (p = 0.001). Patients with a lower lymphocyte counts (< 1.26*10E9/L) were more susceptible to infection (p < 0.001). NK cells were much higher in patients achieving complete remission than those of non-complete remission (p = 0.032). Higher neutrophils and NLR were closely associated with poorer DFS (p = 0.001 and p = 0.045, respectively). Circulating cells in DLBCL patients were dysregulated, featured with increased neutrophils and reduced lymphocytes. Higher NK cells before treatment predicted better therapeutic outcome. Higher neutrophils and NLR can be regarded as inferior prognostic predictors for DLBCL patients at diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Sarcoidosis is a systemic granulomatous disease mainly affecting the lungs and hilomediastinal lymph nodes. It is characterized by non-caseating epithelioid cell granulomas in lymph nodes and lungs. Our study aimed to evaluate and compare T, B and NK cell subsets in the alveolar compartment, lymph nodes and the bloodstream simultaneously in the same patients to elucidate the immune responses associated with the development and progression of sarcoidosis. A secondary aim was to evaluate the distribution of CD45RA-expressing cells in the different anatomical compartments. Patients suspected to have sarcoidosis and who underwent bronchoscopy with bronchoalveolar lavage (BAL), lung-draining lymph node (LLN) biopsy by EBUS-TBNA and peripheral blood (PB) sampling were included in the study. They were monitored at the Regional Referral Centre of Siena University Hospital and the Respiratory Diseases Unit of Perugia Hospital. Multicolour flow cytometry analysis through FASCLyric was performed to assess T, B and NK cell subsets. Thirty-two patients (median age (IQR) 57 (52-58) years) were consecutively and prospectively enrolled. Machine learning analysis created a model which selected CD56dim16bright, CD8, Tfc, Th17, Th12, Tfh17, Tfh2, Tc em RA, Th em RA, T naïve, Tc naïve, Breg, CD1d + CD5 + , Th-reg, Tfh, Th1 and CD4 cells with an accuracy of 0.9500 (kappa 0.8750). Comparative analysis found 18 cell populations that differed significantly between the three anatomical compartments. The bloodstream was enriched in Th em RA ( p = 0.0416), Tfh2 ( p = 0.0189), Tfh17 ( p = 0.0257), Th2 ( p = 0.0212), Th17 ( p = 0.0177), Th-naïve ( p = 0.0368), CD56dimCD16bright ( p < 0.0001), CD8 ( p = 0.0319), Tc em RA ( p < 0.0001) and Tfc cells ( p = 0.0004) compared with the alveolar compartment, while Th-reg were lower in PB than BAL ( p = 0.0329). The alveolar compartment was enriched in Breg ( p = 0.0249) and CD1d + CD5 + ( p = 0.0013) with respect to LLN samples and PB. Conversely, Tfh ( p = 0.0470), Th1 ( p = 0.0322), CD4 ( p = 0.0486) and Tc-naïve ( p = 0.0009) were more abundant in LLN than in BAL and PB. It has been speculated that changes in the relative contents of PB cells could be related to changes in production and to the selective redistribution of PB cells to granulomatous foci. This study further supports the fact that sarcoidosis is multisystemic in nature. However, the low level of immune cells in peripheral blood of patients with sarcoidosis is concerning. A re-expression of CD45RA on CD4 + and CD8 + cells could result in a reduction in peripheral immune activity. Thus, changes in the spectrum of the bloodstream may reflect both pathogenic and compensatory processes.

Introduction: Adenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear., Methods: To identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5)., Results: A significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids., Discussion: This finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Wang, Yang, Shen, Wang, Zhang, Zhang, Li, Gao, Liu, Zhu, Wei, Guan, Su, Liu, Gu and Yin.)

Objective: Colon cancer (CC) are the most common malignant cancer in human digestive system, however, the profile and prognostic value of circulating lymphocyte subsets in CC patients has not been systemically clarified., Methods: In this study, 158 patients with metastatic CC were enrolled. Chi-square test was used to analyze the relationship between baseline peripheral blood lymphocyte subsets and clinicopathological parameters. Kaplan-Meier and Log-rank tests were used to analyze the relationship between clinicopathological parameters and baseline peripheral lymphocyte subsets and overall survival (OS) of patients with metastatic CC. Univariate/multivariate COX regression analysis was used to identify the independent factors in metastatic CC., Results: The baseline peripheral blood CD3+T cells, CD4+T cells, NK cells and B cells of BRAF mutant patients were significantly lower than those in BRAF wild-type patients; The baseline CD8+T cells of KRAS mutation group was lower than that in KRAS wild type group. Peripheral blood CA19-9 > 27, left-sided colon cancer (LCC), KRAS and BRAF mutation were poor prognostic factors, and ALB > 40, NK cells were protective prognostic factors for metastatic CC. In patients with liver metastases subgroup, higher NK cells also indicated a longer OS. Finally, LCC (HR = 0.56), CA19-9 (HR = 2.13), ALB (HR = 0.46) and circulating NK cells (HR = 0.55) were independent prognostic factors for metastatic CC., Conclusion: LCC, higher level of ALB and NK cells at baseline are protective factors, and higher CA19-9, KRAS/BRAF gene mutation are adverse prognostic factors. Sufficient circulating NK cells are independent prognostic factor for metastatic CC patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: This study aimed to make a comprehensive evaluation of peripheral immune profiles for further understanding the immunopathogenesis of severe fever with thrombocytopenia syndrome (SFTS)., Methods: Forty-seven patients with SFTS virus infection were included, of which 24 were deceased. The percentages, absolute numbers, phenotype of lymphocyte subsets were detected by flow cytometry., Results: In patients with SFTS, the numbers of CD3 + T, CD4 + T, CD8 + T and NKT cells were decreased compared with healthy controls (HCs), accompanied with highly active and exhausted phenotypes for T cells, and overproliferating plasmablasts. High inflammatory status, dysregulation of coagulation and host immune response were more obvious in deceased patients than that of survivors. Higher levels of PCT, IL-6, IL-10, TNF-α, APTT, TT and the occurrence of hemophagocytic lymphohistiocytosis were poor prognostic indicators of SFTS., Conclusions: The evaluation of immunological markers in combination with laboratory tests has critical value for selecting prognostic markers and potential treatment target., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: Immune function is associated with clinical outcomes in patients with gastric cancer. This study aimed to explore the prognostic role of peripheral lymphocyte subsets in patients with gastric cancer after curative surgery., Methods: This retrospective study was conducted at a single tertiary referral hospital. We included patients diagnosed with gastric cancer who had undergone surgery and met the inclusion criteria. Clinicopathological characteristics and preoperative peripheral lymphocyte subset data were collected for the analysis. Recurrence-free survival (RFS) and overall survival were analyzed using the Kaplan-Meier curve and Cox hazard regression model. We used the Whitney test and Spearman test to analyze the correlation between lymphocyte subsets and clinicopathological characteristics., Results: This study included 171 patients with gastric cancer who underwent curative surgery. Multivariate analysis revealed that carcinoembryonic antigen (p < 0.01), carbohydrate antigen 19-9 (p < 0.001), lymph node metastases (p < 0.001), total T-cell count (p = 0.02), B-cell count (p < 0.01), and regulatory T-cell percentage (p < 0.01) were independent predictive factors associated with RFS., Conclusions: Impaired immune function may lead to early recurrence following curative surgery. Our study showed that the characteristics of peripheral lymphocyte subsets (T, B, and Treg cells) were independent predictive factors for recurrence in patients with gastric cancer after surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Currently, the relationship between radiation pneumonia (RP) and circulating immune cell in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to explore the relationship between RP and circulating lymphocyte subsets in patients with ESCC receiving chemoradiotherapy (CRT), and develop a nomogram model to predict RP. Since we should implement clinical intervention to ≥ grade 2 RP, a nomogram model for ≥ grade 2 RP was also established to provide an early warning., Patients and Methods: This study retrospectively included 121 patients with ESCC receiving CRT from Guangxi Medical University Cancer Hospital from 2013 to 2021. Independent factors associated with occurrence of RP and ≥ grade 2 RP were identified by univariate and multivariate logistic regression analysis in the training cohort, and incorporated into nomograms. The predictive accuracy and discrimination of the model was assessed using Concordance Index (C-index), calibration curve and decision curve analysis (DCA). And each model was internally validated. Additionally, to verify the optimized predictive performance of the nomograms, the area under the ROC curve (AUC) of each nomogram was compared to that of single independent risk factors, lung V10 and lung V20, respectively. Moreover, each model was further evaluated for risk stratification to identify populations at high risk of RP and ≥ grade 2 RP., Results: Multivariate analysis suggested that TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were independent predictive factors of RP. Besides, pre- and post-RT percentage of CD8+ T cell, and V15 were independent factors of ≥ grade 2 RP. The C-indexes of RP and ≥ grade 2 RP nomograms were 0.809 (95% CI: 0.715-0.903) and 0.787 (95% CI: 0.685-0.889) in the training cohort, respectively. And the C-indexes of RP and ≥ grade 2 RP nomograms were 0.718 (95% CI: 0.544-0.892) and 0.621 (95% CI: 0.404-0.837) in the validation cohort, respectively. The calibration curves showed that the predicted values of model agreed well with actual observations. Moreover, DCA results indicated the applicability and accuracy of the models to predict RP and ≥ grade 2 RP. After stratification, the incidence of the high-risk group was significantly higher than that of the low-risk group with respect to either RP or ≥ grade 2 RP., Conclusion: TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were the independent predictors of RP toxicity. Pre- and post-RT percentage of CD8+ T cell, and lung V15 were the independent factors of ≥ grade 2 RP toxicity. The nomograms based on circulating lymphocyte subsets can robustly predict RP and ≥ grade 2 RP, guiding clinicians in risk stratification and early intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Tao, Liang, Chen, Liu, Jiang and Chen.)

Background: Non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients' response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy., Methods: To explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs., Results: The two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4 + CD45RA - T cell (HR = 0.644, P = 0.047) and CD8 + T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4 + CD45RA - T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4 + CD45RA - T cell >311.3 × 10 6 /L as the threshold. In contrast, CD8 + T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4 + T cell and its subsets were significantly higher in patients with mild (grades 1-2) immune-related adverse events (irAEs) than those without irAEs. CD8 + CD38 + T cell was associated with total irAEs and severe (grades 3-4) irAEs but was not suitable to be a predictive biomarker., Conclusion: Peripheral blood CD4 + CD45RA - T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8 + CD38 + T cell was associated with irAEs and severe irAEs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer J-LL declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Miao, Zhang, Wang, Si, Ni, Zhong, Zhao, Xu, Chen, Pan, Wang and Zhang.)

Background: Nasopharyngeal carcinoma (NPC) is a geographically and racially variable disease that has a high incidence in Southeast China. According to previous studies on tumor immunity, we compared multiple clinical parameters and blood indexes with outcomes regarding to Epstein-Barr virus (EBV) status in NPC patients., Methods: According to the EBV load at diagnosis, 220 NPC patients who received concurrent chemoradiotherapy (CRT) were divided into two groups: EBV DNA ≥ 1500 copies/mL and EBV DNA < 1500 copies/mL, respectively. We compared clinical parameters with peripheral blood mononuclear cells, lymphocyte subsets and biochemical indexes. We also analyzed distant metastases and the overall survival rate regarding to these characteristics., Results: In most cases, the two groups showed the same trends. Most blood indexes were decreased during CRT and the decrease of the absolute count was more significant than the percentage. Patients with younger age showed the higher CD3+ and CD3 + CD8+ percentages. Patients whose EBV DNA ≥ 1500 copies/mL showed a higher N classification than those with EBV DNA < 1500 copies/mL at first diagnosis. Within patients with EBV DNA ≥ 1500 copies/mL, a higher CD3 + CD8+ percentage or lower CD3-CD56+ percentage had better OS rates, and the CD3 + CD8+ percentage was an independent prognostic factor by multivariate survival analyses., Conclusions: CRT caused an overall decrease of blood cells in NPC patients. Among all the blood indexes, the CD3 + CD8+ percentage showed a correlation with age and was an independent prognostic factor in patients with EBV DNA ≥ 1500 copies/mL at first diagnosis, which is worthy for further large cohort study., (© 2022. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) have achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore biomarkers that could predict the survival outcomes and therapeutic efficacy in advanced NSCLC patients treated with immunotherapy. In this study, we aimed to assess the changes in peripheral blood lymphocyte subsets and their association with the therapeutic efficacy and clinical prognosis of advanced NSCLC patients treated with immunotherapy., Methods: A total of 276 patients with advanced NSCLC were enrolled. Peripheral blood lymphocyte subsets including CD4 + T cells, CD8 + T cells, CD4 + /CD8 + ratio, NK cells, Tregs and B cells were collected before any treatment, before immunotherapy or chemotherapy, and after 4 cycles of immunotherapy or chemotherapy. T-test was used to analyze the factors influencing lymphocyte subsets and their changes before and after therapy. Logistic regression was used to plot ROC curves and analyze the relationship between lymphocyte subsets and therapeutic efficacy. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subsets and progression-free survival (PFS)., Results: Gender, distant metastasis, and EGFR mutation status are known to affect the proportion of peripheral blood lymphocyte subsets in patients with advanced NSCLC. The proportions of CD4 + T cells, CD8 + T cells, Tregs and B cells were found to decrease after chemotherapy as compared to the baseline. The proportion of CD4 + T cells, CD8 + T cells, CD4 + /CD8 + ratio, NK cells and Tregs were higher after immunotherapy than after chemotherapy. Compared to the baseline, the effective group showed significant increase in the proportions of CD4 + T cells, CD4 + /CD8 + ratio, NK cells and Tregs, and the number of CD8 + T cells was significantly lower in the peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group did not show any significant differences in the above parameters. Baseline CD4 + T cells and NK cells were independent predictors of immunotherapy efficacy and PFS. Baseline Tregs were independent predictor of immunotherapy efficacy., Conclusion: Immune checkpoint inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy. The levels of the different lymphocyte subsets could serve as valuable predictive biomarkers of efficacy and clinical prognosis for NSCLC patients treated with immunotherapy., (© 2022. The Author(s).)