Stk11-loss in lung adenocarcinoma is associated with an expansion of gd T cells with pro-tumor and immunosuppressive potential 3868

Abstract Description gd T cells are innate-like T lymphocytes that play critical roles in tumor surveillance, and have been demonstrated to both promote tumor growth/metastasis and efficiently kill tumor cells. Specifically, gdT1 subsets have been associated with anti-tumor immunity, while gdT17 subsets have been associated with tumor growth and metastasis. However, the factors that control the selective activation of gdT1 vs. gdT17 in the tumor microenvironment remain unclear, as are the mechanisms through which gdT17 promote tumor growth/metastasis. To explore these questions, we developed an inducible mouse model of Kras-driven lung adenocarcinoma with or without a lung club cell-specific deletion of the Stk11 tumor suppressor. Upon induction of tumorigenesis, KrasG12D/Stk11fl mice exhibited significantly greater mortality than KrasG12D mice. Interestingly, the increased mortality in the KrasG12D/Stk11fl mice was associated with a selective expansion of Vg4 and Vg6 gdT17 subsets in the lungs of these mice. Characterization of these gd T cells using scCITEseq, revealed the presence of significant transcriptional heterogeneity in the gdT17 subsets that was associated with a significant expansion of a novel Il2ra+Ctla4+Areg+ Vg6 gdT17 subset in KrasG12D/Stk11fl lungs. Together these data suggest that tumor-specific Stk11 loss leads to the expansion of a novel subset of gdT17 cells with pro-tumor and immunosuppressive potential. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)