Expression of PD-1 by T cells in malignant glioma patients reflects exhaustion and activation.

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Expression of PD-1 by T cells in malignant glioma patients reflects exhaustion and activation.

Clin Cancer Res. 2018 Nov 29;:

Authors: Davidson TB, Lee AH, Hsu M, Sedighim S, Orpilla J, Treger J, Mastall M, Roesch S, Rapp C, Galvez M, Mochizuki AY, Antonios JP, Garcia AJ, Kotecha N, Bayless NL, Nathanson DA, Wang AC, Everson RG, Yong WH, Cloughesy TF, Liau LM, Herold-Mende CC, Prins RM

Abstract
PURPOSE: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent pre-clinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective anti-tumor T cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in malignant glioma patients.
EXPERIMENTAL DESIGN: In this study, we examined the immune landscape and function of PD-1 expression on T cells from the tumor and peripheral blood in malignant glioma patients.
RESULTS: We found several differences between PD-1+ tumor-infiltrating lymphocytes (TILs) and patient-matched PD-1+ peripheral blood T lymphocytes. Phenotypically, PD-1+ TILs exhibited higher expression of markers of activation and exhaustion than peripheral blood PD-1+ T cells, which instead had increased markers of memory. A comparison of the T cell receptor variable chain populations revealed decreased diversity in T cells that expressed PD-1, regardless of the location obtained. Functionally, peripheral blood PD-1+ T cells had a significantly increased proliferative capacity upon activation compared with PD-1- T cells.
CONCLUSION: Our evidence suggests that PD-1 expression in glioma patients reflects chronically-activated effector T cells that display hallmarks of memory and exhaustion depending on its anatomical location. The decreased diversity in PD-1+ T cells suggests that the PD-1 expressing population has a narrower range of cognate antigen targets compared to the PD-1 non-expression population. This information can be used to inform how we interpret immune responses to PD-1 blocking therapies or other immunotherapies.

PMID: 30498094 [PubMed - as supplied by publisher]

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