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The present study was designed to evaluate the percentage of different programmed cell death‐1 (PD‐1)+ T cell subsets in peripheral blood and bronchoalveolar lavage fluid (BALF) of small cell lung cancer (SCLC) patients. The percentages of PD‐1+ T cell subsets in peripheral blood and BALF samples obtained from 52 lung cancer and 20 pneumonia patients, and 20 healthy controls were examined by flow cytometry. In addition, clinical parameters, such as erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) levels, were also determined using Spearman's correlation test to assess their association with PD‐1+ T cell subsets. These present results revealed that the percentage of circulating PD‐1+ Tfh and peripheral helper T cells (Tph) cells significantly increased in peripheral blood of SCLC patients, when compared to non‐small cell lung cancer (NSCLC) pneumonia patients and healthy controls. In addition, PD‐1+ Tfh cells were also significantly enhanced in patients in the extensive‐stage group. In contrast, the BALF samples of SCLC patients exhibited a significant decrease in percentage of Tph cells. An overall imbalance was observed between PD‐1+Tfh and Tph cells in both compartments. Furthermore, SCLC patients exhibited a significant decrease in the percentage of circulating PD‐1+ Tfh and Tph cells following chemotherapy, and the in vitro analysis revealed that the concentration of IL‐2 and IFN‐γ derived from PD‐1 + Tfh cells in SCLC were significantly lower than that from NSCLC. However, this had no significant correlation with disease severity. The present study indicated that elevated circulating PD‐1+ T cells can primarily be used as a biomarker for disease diagnosis and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: T follicular helper (Tfh) cells are known to regulate humoral immune response. In this study we examined the correlation of different subsets of peripheral blood Tfh cells in patients with diabetic nephropathy (DN).Methods: A total of 23 DN patients and 15 healthy controls (HC) were investigated for various subsets of Tfh cells by flow cytometry. The molecules ICOS+, PD-1+, CD28+, CD154+, IL-21+, IFN-γ+, IL-4+, IL-17+Tfh cells were examined. The subsets of B cells were investigated by flow cytometry. The levels of 24 h urinary protein and estimated glomerular filtration rate (eGFR) were calculated. A potential correlation between the number of different subsets of Tfh cells, B cells and DN, was assessed.Results: The circulating CD4+CXCR5+PD-1+, PD-1+CD154+, PD-1+CD28+, PD-1+IL-21+, PD-1+IL-4+, PD-1+-IL-17+-Tfh cell counts, CD38+CD19+, CD38+CD19+CD40+B cells and plasma levels of IL-21 were significantly increased in DN patients (p < 0.05), as compared to that in the HC group. Furthermore, the circulating CD4+CXCR5+PD-1+Tfh cell counts negatively correlated with eGFR; Tfh cell counts positively correlated with 24 h urinary protein concentration in DN patients. Post-treatment, there was a significant reduction in the CD4+CXCR5+PD-1+Tfh cell counts and its subsets, with a corresponding decrease in plasma levels of IL-6 and IL-17A (p < 0.05) in DN patients, as compared to the HCs.Conclusion: An increased number of CD4+CXCR5+PD-1+Tfh cells were observed in DN patients, which may be new targets for intervention in DN. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has opened up a new era of individualized treatment for non-small cell lung cancer (NSCLC) with negative driver gene mutations. Anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies have been the main options for immunotherapy over the past decade. Screening for predictive markers of anti-PD-1/PD-L1-responsive patients remains a focus in the field of immunotherapy, especially on the protein level in which relevant proteomic biomarkers are still lacking., Methods: We collected samples from 23 patients with NSCLC who received anti-PD-1/PD-L1 monotherapy and were followed up for three years. The proteomic profile of the tumor was obtained by mass spectrometry (MS). Meanwhile, we combined the RNA sequencing (RNA-seq) data of 27 patients treated with anti-PD-1/PD-L1 therapy in a previous study to establish an integrated gene network. Weighted correlation network analysis (WGCNA) and elastic network were implemented to screen the top gene modules for predicting treatment-responsive patients. Gene expression related mutational patterns were also retrieved for validation in the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort., Results: Our results showed the gene expression profile of MOXD1 , PHAF1 , KRT7 , ANKRD30A , TMEM184A , KIR3DL1 , and KCNK4 could better predict the durable response to anti-PD-1/PD-L1 therapy, with the specificity and sensitivity of 0.76 and 0.6, respectively. Besides, the mutational gene profile associated with these genes also suggested an association with favorable response in the MSKCC cohort. Patient-specific protein-protein interaction (PPI) network also indicated strong correlation among KRT7 , TMEM184A and ANKRD30A ., Conclusions: Our study indicated that key gene signatures identified by machine learning model could be utilized for clinical screening of patients who might benefit from anti-PD-1 therapy. Further mechanistic investigations around these genes are warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-713/coif). C.Z. serves as an Editor-in-Chief of Translational Lung Cancer Research. He also reports that this study was funded by Shanghai Key Clinical Specialty Construction Project—Respiratory Medicine (201912-0552). The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Purpose: CD4 + CD25 + Foxp3 + regulatory T (Treg) cell-mediated immunosuppression has been implicated as a crucial mechanism of tumor immune cell escape in nonsmall cell lung cancer (NSCLC). However, little is known concerning the specific role of CD4 + CD25 - Foxp3 + Treg cells in NSCLC. The aim of this study was to investigate the frequency of circulating CD4 + CD25 - Foxp3 + Treg cells and their role in NSCLC. Methods: The frequencies of Treg, T helper (Th)1, Th2, and Th17 cells in peripheral blood were separately measured in 36 NSCLC patients and 20 healthy controls (HCs) using flow cytometry. Serum cytokine concentrations were determined using cytometric bead arrays. Results: The frequencies of circulating CD4 + CD25 + T cells and CD4 + CD25 + Foxp3 + and CD4 + CD25 - Foxp3 + Treg cells were significantly higher in advanced-stage NSCLC patients compared with patients with limited-stage NSCLC. The frequencies of circulating CD4 + CD25 + Foxp3 + and CD4 + CD25 - Foxp3 + Treg cells were negatively correlated with interleukin (IL)-17, but positively correlated with serum IL-10 levels. In addition, the Th17/CD4 + CD25 - Foxp3 + Treg cell ratios were negatively correlated with serum cytokeratin 19 fragment (CYFRA 21-1) concentrations in patients with NSCLC. Moreover, coculturing CD4 + CD25 - Foxp3 + Treg cells and CD14 + monocytes in vitro resulted in a higher frequency of CD206 + CD14 + M2-like monocytes compared with CD14 + monocytes. Conclusions: Elevated circulating CD4 + CD25 - Foxp3 + Treg cells may be involved in the pathogenesis of NSCLC.

Background: T follicular helper (Tfh) cells are known to regulate humoral immune response. In this study we examined the correlation of different subsets of peripheral blood Tfh cells in patients with diabetic nephropathy (DN)., Methods: A total of 23 DN patients and 15 healthy controls (HC) were investigated for various subsets of Tfh cells by flow cytometry. The molecules ICOS + , PD-1 + , CD28 + , CD154 + , IL-21 + , IFN-γ + , IL-4 + , IL-17 + Tfh cells were examined. The subsets of B cells were investigated by flow cytometry. The levels of 24 h urinary protein and estimated glomerular filtration rate (eGFR) were calculated. A potential correlation between the number of different subsets of Tfh cells, B cells and DN, was assessed., Results: The circulating CD4 + CXCR5 + PD-1 + , PD-1 + CD154 + , PD-1 + CD28 + , PD-1 + IL-21 + , PD-1 + IL-4 + , PD-1 + -IL-17 + -Tfh cell counts, CD38 + CD19 + , CD38 + CD19 + CD40 + B cells and plasma levels of IL-21 were significantly increased in DN patients (p < 0.05), as compared to that in the HC group. Furthermore, the circulating CD4 + CXCR5 + PD-1 + Tfh cell counts negatively correlated with eGFR; Tfh cell counts positively correlated with 24 h urinary protein concentration in DN patients. Post-treatment, there was a significant reduction in the CD4 + CXCR5 + PD-1 + Tfh cell counts and its subsets, with a corresponding decrease in plasma levels of IL-6 and IL-17A (p < 0.05) in DN patients, as compared to the HCs., Conclusion: An increased number of CD4 + CXCR5 + PD-1 + Tfh cells were observed in DN patients, which may be new targets for intervention in DN.

T follicular helper (TFH) cells play an important role in the humoral immune responses. The aim of this study was to examine the frequency of different subsets of CD4(+)CXCR5(+) TFH cells and B cells in patients with new-onset Henoch-Schönlein purpura nephritis (HSPN). The numbers of different subsets of CD4(+)CXCR5(+) TFH cells, B cells and the constituents of serum cytokines were detected in a total of 25 patients with newly diagnosed HSPN before and after treatment, and in 14 healthy controls (HC). The potential connection of these cells with the clinical characteristics in HSPN patients was analyzed. The numbers of circulating CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+) and CD4(+)CXCR5(+)PD-1(+) TFH cells, CD86(+)CD19(+), CD38(+)CD19(+) B cells and serum IL-2, IL-4, IL-17A, IL-21 and IFN-γ were significantly higher in HSPN patients (p<0.05) than in HC. Before and after treatment the numbers of CD4(+)CXCR5(+) TFH cells were negatively correlated with the values of eGFR (r=-0.7162, p<0.05; r=-0.732, p<0.05, respectively). Similarly the numbers of CD4(+)CXCR5(+)PD-1(+) TFH cells were negatively correlated with 24-h urinary proteins (r=-0.4013, p<0.05; r=-0.7857, p<0.05, respectively), and the numbers of CD4(+)CXCR5(+)ICOS(+) TFH cells were positively correlated with the levels of serum IL-21 (r=0.5186, p<0.05; r=0.8503, p<0.05, respectively) and 24-h urinary protein (r=0.6045, p<0.05; r=0.833, p<0.05, respectively) in these patients, regardless of treatment. Following treatment the numbers of CD4(+)CXCR5(+), CD4(+)CXCR5(+)PD-1(+), and CD4(+)CXCR5(+)ICOS(+) TFH cells, as well as serum levels of IL-21 were significantly reduced, however IL-4 levels were noticeably increased (p<0.05). A higher frequency of circulating CD4(+)CXCR5(+) TFH cells existed in patients with HSPN and may be a viable therapeutic target., (Copyright © 2016 Elsevier B.V. All rights reserved.)