PD-1 regulates CXCR5+ CD4 T cell-mediated proinflammatory functions in non-small cell lung cancer patients |
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| Institution: | 1. Department of Oncology, PLA General Hospital, Beijing, China;2. Department of Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;1. Institute of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China;2. Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China;3. Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China;4. Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China;5. Department of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China;1. Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece;;2. Bone Marrow Transplantation Unit and FACS Laboratory, University Hospital of Patras, Patras, Greece;;3. The Center for the Study of Haematological Malignancies, Nicosia, Cyprus;;4. General Hospital of Patras “Agios Andreas,” Patras, Greece;;5. Specialist Physician Haematologist, Patras, Greece;1. Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China;2. Department of Oncology, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China;3. Department of Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, PR China;4. Department of Medicine, Nantong University Xinling College, Nantong, Jiangsu 226001, PR China;1. Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind;2. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind |
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| Abstract: | PD-1 inhibitors have been used to revive exhausted T cell responses in non-small cell lung cancer (NSCLC) and other malignancies. CXCR5+ T follicular helper (Tfh) cells are characterized by constitutive high PD-1 expression and have been associated with the formation of tertiary lymphoid structures and implicated in antitumor immunity. In this study, we investigated the effect of PD-1 and PD-1 inhibition on CXCR5+ CD4 T cells. Data showed that CXCR5+ CD4 T cells in both healthy subjects and NSCLC patients presented markedly higher PD-1 expression than CXCR5? CD4 T cells. Both CXCR5? and CXCR5+ CD4 T cells from NSCLC patients presented higher PD-1 expression than their counterparts in healthy subjects. PD-1+ CXCR5+ CD4 T cells were functional, could express IL-21, IL-10, and CXCL13 upon stimulation, demonstrated auxiliary effects toward CD8 T cell-mediated IFN-γ production and proliferation, and promoted IgM and IgG production. However, the potency of PD-1+ CXCR5+ CD4 T cells was lower than the potency of PD-1? CXCR5+ CD4 T cells. PD-1 blocking could significantly enhance the effector functions of PD-1+ CXCR5+ CD4 T cells. Overall, this study demonstrated that PD-1+ CXCR5+ CD4 T cells could promote CD8 T cell and B cell inflammation and could be modulated by PD-1 inhibition. |
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| Keywords: | PD-1 Tfh cell Non-small cell lung cancer |
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