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posted on 2023-03-31, 21:03 authored by Tom B. Davidson, Alexander Lee, Melody Hsu, Shaina Sedighim, Joey Orpilla, Janet Treger, Max Mastall, Saskia Roesch, Carmen Rapp, Mildred Galvez, Aaron Mochizuki, Joseph Antonios, Alejandro Garcia, Nikesh Kotecha, Nicholas Bayless, David Nathanson, Anthony Wang, Richard Everson, William H. Yong, Timothy F. Cloughesy, Linda M. Liau, Christel Herold-Mende, Robert M. Prins <p>Supplementary Figure 1: T cells from GBM patient TILs show highest expression of PD-1 compared to healthy donor PBMC and GBM patient PBMCs A) A representative flow cytometry plot measuring PD-1+ expression on CD4+ and CD8+ T cells from Healthy Donor PBMC, glioma Patient PBMC, and glioma patient TILs. B) Percent of PD-1 expression on CD4+ T cells from all the patient samples as measured by flow cytometry. C) Percent of PD-1 expression on CD8+ T cell from all the patient samples as measured by flow cytometry.</p>
Funding
NIH
NCI
UCLA
PICI
Musella Foundation For Brain Tumor Research
Joseph Drown Foundation
USHHS Ruth L. Kirschstein Institutional National Research Service
History
ARTICLE ABSTRACT
Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent preclinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective antitumor T-cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in patients with malignant glioma.Experimental Design: In this study, we examined the immune landscape and function of PD-1 expression by T cells from tumor and peripheral blood in patients with malignant glioma.
We found several differences between PD-1+ tumor-infiltrating lymphocytes (TIL) 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.
Our evidence suggests that PD-1 expression in patients with glioma reflects chronically activated effector T cells that display hallmarks of memory and exhaustion depending on its anatomic 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 with the PD-1 nonexpression population. This information can be used to inform how we interpret immune responses to PD-1–blocking therapies or other immunotherapies.
