Human CXCR5+PD-1+ CD8 T cells in healthy individuals and patients with hematologic malignancies
| العنوان: | Human CXCR5+PD-1+ CD8 T cells in healthy individuals and patients with hematologic malignancies |
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| المؤلفون: | Mark-David Levin, Sanne H. Tonino, Sjoerd T.T. Schetters, Ester B. M. Remmerswaal, Adriaan D. Bins, Frederike J. Bemelman, Arnon P. Kater, Renate de Boer, Tom Hofland, Anne W. J. Martens, Eric Eldering, Jaco A. C. van Bruggen |
| المساهمون: | Graduate School, AII - Cancer immunology, CCA - Cancer biology and immunology, AII - Amsterdam institute for Infection and Immunity, Experimental Immunology, Nephrology, APH - Aging & Later Life, Oncology, Clinical Haematology, CCA - Cancer Treatment and Quality of Life |
| المصدر: | European Journal of Immunology European journal of immunology, 51(3), 703-713. Wiley-VCH Verlag |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Receptors, CXCR5, Chronic lymphocytic leukemia, PD-1 immunotherapy, Immunology, Programmed Cell Death 1 Receptor, Stimulation, CD8 T cells, Biology, CD8-Positive T-Lymphocytes, CXCR5, 03 medical and health sciences, Clinical, 0302 clinical medicine, PD‐1 immunotherapy, medicine, Immunology and Allergy, Cytotoxic T cell, Humans, Aged, Aged, 80 and over, Effector, Research Article|Clinical, Cell Differentiation, Middle Aged, immune checkpoint blockade, medicine.disease, Phenotype, Leukemia, Lymphocytic, Chronic, B-Cell, Immune checkpoint, 030104 developmental biology, Hematologic Neoplasms, Cancer research, Tumor immunology, Female, Lymph, Lymph Nodes, Immunologic Memory, 030215 immunology, Research Article |
| الوصف: | Immune checkpoint blockade (ICB) has revolutionized cancer therapy, but varying response rates illustrate the need for biomarkers of response. Studies in mice have identified a subset of CD8 T cells that is essential for response to PD‐1 ICB. These CD8 T cells co‐express CXCR5, PD‐1 and Tcf1, and provide effector T cells upon PD‐1 ICB. It is unknown whether similar T cells play a role in PD‐1 ICB in humans. We studied human peripheral blood and lymph nodes (LNs) for the frequency, phenotype, and functionality of CXCR5+PD‐1+ CD8 T cells. We find that CXCR5+PD‐1+ CD8 T cells are memory‐like cells, express Tcf1, and lack expression of effector molecules. CXCR5+PD‐1+ CD8 T cells produce cytokines upon stimulation, but have limited proliferative capacity. We studied patients with hematologic malignancies with varying response rates to PD‐1 ICB. Specifically in chronic lymphocytic leukemia, in which PD‐1 ICB does not induce clinical responses, CXCR5+PD‐1+ CD8 T cells show loss of the memory phenotype and increased effector differentiation. In conclusion, we identified CXCR5+PD‐1+ CD8 T cells in human peripheral blood and LN, which could play a similar role during PD‐1 ICB. Future studies should analyze CXCR5+PD‐1+ CD8 T cells during PD‐1 ICB and their importance for therapeutic response. CXCR5+PD‐1+ CD8 T cells respond to PD‐1 immune checkpoint blockade in mice. In healthy individuals, human CXCR5+PD‐1+ CD8 T cells have a similar memory phenotype and functionality. In CLL patients, where PD‐1 blockade does not induce therapeutic responses, CXCR5+PD‐1+ CD8 T cells show increased differentiation and altered functionality. |
| اللغة: | English |
| تدمد: | 0014-2980 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e54714957e1ea10a7a855bd9a6c9aaa0Test https://doi.org/10.1002/eji.202048761Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e54714957e1ea10a7a855bd9a6c9aaa0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00142980 |
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