PVRIG is Expressed on Stem-Like T Cells in Dendritic Cell-Rich Niches in Tumors and Its Blockade May Induce Immune Infiltration in Non-Inflamed Tumors.

Autor:	Alteber Z; Compugen Ltd., Holon, Israel., Cojocaru G; Compugen Ltd., Holon, Israel., Granit RZ; Compugen Ltd., Holon, Israel., Barbiro I; Compugen Ltd., Holon, Israel., Wool A; Compugen Ltd., Holon, Israel., Frenkel M; Compugen Ltd., Holon, Israel., Novik A; Compugen Ltd., Holon, Israel., Shuchami A; Compugen Ltd., Holon, Israel., Liang Y; Compugen Ltd., Holon, Israel., Carmi VD; Compugen Ltd., Holon, Israel., Sabath N; Compugen Ltd., Holon, Israel., Foreman R; Vizgen Inc., Cambridge, Massachusetts., Petrenko N; Vizgen Inc., Cambridge, Massachusetts., He J; Vizgen Inc., Cambridge, Massachusetts., Kliger Y; Compugen Ltd., Holon, Israel., Levy-Barda A; Biobank, Department of Pathology, Rabin Medical Center, Petah Tikva, Israel., Eitan R; The Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Gynecologic Oncology Division, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel., Raban O; The Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Gynecologic Oncology Division, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel., Sadot E; The Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Department of Surgery, Rabin Medical Center, Petach Tikva, Israel., Sulimani O; The Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Department of Surgery, Rabin Medical Center, Petach Tikva, Israel., Nathan AA; Department of Pathology, Rabin Medical Center, Petach Tikva, Israel., Adewoye H; Compugen USA, Inc., South San Francisco, California., Ferre P; Compugen Ltd., Holon, Israel., Levine Z; Compugen Ltd., Holon, Israel., Ophir E; Compugen Ltd., Holon, Israel.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2024 Jul 02; Vol. 12 (7), pp. 876-890.
DOI:	10.1158/2326-6066.CIR-23-0752
Abstrakt:	Cancers that are poorly immune infiltrated pose a substantial challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as a subgroup of T cells that possess strong proliferative capacity and that can expand and differentiate following interactions with dendritic cells (DCs). In this study, we explored the pattern of expression of a recently discovered inhibitory receptor poliovirus receptor-related immunoglobulin domain protein (PVRIG) and its ligand, poliovirus receptor-related ligand 2 (PVRL2), in the human tumor microenvironment. Using spatial and single-cell RNA transcriptomics data across diverse cancer indications, we found that among the T-cell checkpoints, PVRIG is uniquely expressed on TSCM and PVRL2 is expressed on DCs in immune aggregate niches in tumors. PVRIG blockade could therefore enhance TSCM-DC interactions and efficiently drive T-cell infiltration to tumors. Consistent with these data, following PVRIG blockade in patients with poorly infiltrated tumors, we observed immune modulation including increased tumor T-cell infiltration, T-cell receptor (TCR) clonality, and intratumoral T-cell expansion, all of which were associated with clinical benefit. These data suggest PVRIG blockade as a promising strategy to induce potent antitumor T-cell responses, providing a novel approach to overcome resistance to immunotherapy in immune-excluded tumors. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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