American Association for Cancer Research
cir-23-0752_supplementary_figure_10_supps10.pdf (175.38 kB)

Supplementary Figure 10 from 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

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journal contribution
posted on 2024-07-02, 07:22 authored by Zoya Alteber, Gady Cojocaru, Roy Z. Granit, Inbal Barbiro, Assaf Wool, Masha Frenkel, Amit Novik, Adi Shuchami, Yu Liang, Vered D. Carmi, Niv Sabath, Rob Foreman, Natalia Petrenko, Jiang He, Yossef Kliger, Adva Levy-Barda, Ram Eitan, Oded Raban, Eran Sadot, Omri Sulimani, Abraham Avi Nathan, Henry Adewoye, Pierre Ferre, Zurit Levine, Eran Ophir

Supplementary Figure 10



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.