Human CXCR5 + PD-1 + CD8 T cells in healthy individuals and patients with hematologic malignancies.

Autor: Hofland T; Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Martens AWJ; Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., van Bruggen JAC; Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., de Boer R; Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Schetters S; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Amsterdam, The Netherlands., Remmerswaal EBM; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Renal Transplant Unit, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Bemelman FJ; Renal Transplant Unit, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Levin MD; Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands., Bins AD; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Eldering E; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Lymphoma and Myeloma Center Amsterdam, LYMMCARE, Amsterdam, The Netherlands., Kater AP; Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Lymphoma and Myeloma Center Amsterdam, LYMMCARE, Amsterdam, The Netherlands., Tonino SH; Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Lymphoma and Myeloma Center Amsterdam, LYMMCARE, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2021 Mar; Vol. 51 (3), pp. 703-713. Date of Electronic Publication: 2020 Nov 23.
DOI: 10.1002/eji.202048761
Abstrakt: 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.
(© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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