Abstract 4148: Non-redundant upregulation of CD112R (PVRIG) and PD-1 on cytotoxic T-lymphocytes located in T-cell-nests of colorectal cancer

Abstract

Abstract Focal T-lymphocyte aggregates occur commonly in colorectal cancer, but their biological significance is unknown. To study focal aggregates of T-lymphocytes, a deep learning-based framework for automated identification of T-cell accumulations (T-cell-nests) was developed using CD8, PD-1, CD112R, and Ki67 multiplex fluorescence immunohistochemistry. To evaluate the clinical significance of these parameters, a cohort of 523 colorectal cancers with clinical-follow up data was analyzed. The spatial analysis of locally enriched CD8+ T-cell densities and cell-to-cell contacts identified T-cell-nests in the tumor microenvironment of colorectal cancer. CD112R and PD-1 expression on CD8+ T-cells located in T-cell-nests was found elevated as compared to CD8+ T-cells in all other tumor compartments (p<0.001 each). Although the highest mean CD112R expression on CD8+ T-cells was observed at the invasive margin, the PD-1 expression on CD8+ T-cells was elevated in the center of the tumor (p<0.001 each). Across all tissue compartments, proliferating CD8+ T-cells showed higher relative CD112R and PD-1 expression compared to non-proliferating CD8+ T-cells (p<0.001 each). Integration of all available spatial and immune checkpoint expression parameters (AUC: 0.65) revealed a superior predictive performance for overall survival compared to the commonly used CD8+ TILs density (AUC 0.57, p<0.001). Cytotoxic T-cells with elevated CD112R and PD-1 expression levels are orchestrated in T-cells-nests of colorectal cancer, predict favorable patient’s outcome and the spatial non-redundancy underlies fundamental differences of both inhibitory immune checkpoints that provide a rationale for dual anti-CD112R/PD-1 immune checkpoint therapy. Citation Format: Maximilian Lennartz, Cheng Yang, Tim Mandelkow, Elena Bady, Ronald Simon, Claudia Hube-Magg, Guido Sauter, Niclas C. Blessin. Non-redundant upregulation of CD112R (PVRIG) and PD-1 on cytotoxic T-lymphocytes located in T-cell-nests of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4148.