TY - JOUR
T1 - Human CXCR5+PD-1+ CD8 T cells in healthy individuals and patients with hematologic malignancies
AU - Hofland, Tom
AU - Martens, Anne W. J.
AU - van Bruggen, Jaco A. C.
AU - de Boer, Renate
AU - Schetters, Sjoerd
AU - Remmerswaal, Ester B. M.
AU - Bemelman, Frederike J.
AU - Levin, Mark-David
AU - Bins, Adriaan D.
AU - Eldering, Eric
AU - Kater, Arnon P.
AU - Tonino, Sanne H.
N1 - Funding Information: This project was supported by a Netherlands Organization for Scientific Research/ZonMW VIDI grant (91715337, A.P.K.). Publisher Copyright: © 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - CXCR5
KW - PD-1 immunotherapy
KW - immune checkpoint blockade
UR - http://www.scopus.com/inward/record.url?scp=85096698727&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/eji.202048761
DO - https://doi.org/10.1002/eji.202048761
M3 - Article
C2 - 33098668
SN - 0014-2980
VL - 51
SP - 703
EP - 713
JO - European journal of immunology
JF - European journal of immunology
IS - 3
ER -