Abstract 7389: Evaluation of tumor-infiltrating γδ T cells across solid tumor indications

Abstract The tumor microenvironment is a complex heterogeneous cellular mixture containing not only tumor cells, but also immune cells, fibroblasts, and endothelial cells. Based on numerous factors, including cellular subtype and activation, these cell types can have both tumor-promoting and tumor-eradicating activities. We have previously analyzed both intra-tumoral αβ T cells and B cells using a combination of flow cytometry and single cell transcriptomics across solid tumor indications such as bladder, colorectal, endometrial, lung, ovarian, prostate, and renal cancer using human dissociated tumor cells (DTCs). αβ T cells represented the largest tumor-infiltrating lymphocyte (TIL) subset, and the majority of αβ T cells were in an exhausted state based on high surface expression of inhibitory receptors such as PD1 and TIGIT. Across all indications, B cells were the next most prevalent TIL subset, although indication-specific differences were observed. Overall, like αβ T cells, intra-tumoral B cells had an exhausted phenotype, and a high proportion of these B cells were plasmablasts.γδ T cells represent an attractive candidate for immunomodulation as they recognize their cognate antigens in an HLA-independent manner and have intrinsic cytotoxic potential. Previous studies utilized large scale bulk transcriptomics inferred a substantial percentage of γδ T cells across several solid tumor indications. Further studies in melanoma and colorectal cancer analyzed the activation status and Vδ1/2 usage of intra-tumoral γδ T cells; however, a fully comprehensive evaluation and comparison of γδ T cell activation status, Vγ/Vδ usage, and putative γδ T cell ligand expression across numerous indications remains unstudied. We have now utilized DTCs across twelve solid tumor indications to analyze the relative percentages of γδ T cells, including their Vγ chain and Vδ chain usage. The naïve versus memory phenotype of the γδ T cells and the surface expression of exhaustion and natural cytotoxicity receptors were also evaluated. Finally, the expression of γδ T cell ligands, such as stress receptors and butyrophilins, on the tumor cells was assessed. Collectively, these studies provide crucial insight into the indication-specific γδ T cell composition to inform future γδ T cell-mediated immunotherapies. Citation Format: Shawn P. Fahl, Cavin Ott, Kerri Colwell, Kayla Williams, Audrey Kleeman, Jessica Maxwell. Evaluation of tumor-infiltrating γδ T cells across solid tumor indications abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7389.