LAUSR

The tumor suppressor gene, LKB1/STK11, is one of the most frequently mutated genes in lung adenocarcinoma (LUAD). A multidimensional analysis of TCGA-LUAD patient data indicates that LKB1 mutation is one of the top sex-biased mutations, being more frequent in males than in females. A similar pattern was observed in other large LUAD cohorts. However, the underlying mechanism was unknown, partially due to a lack of an appropriate mouse model to represent this clinical phenomenon. We previously demonstrated a similar sex bias in a Lenti-Cre-induced KRAS/LKB1-mutant genetically engineered mouse model (GEMM) and a syngeneic tail-vein injection model. Here, we demonstrated that intravenous injection of the same cell line in male and female NOD scid gamma (NSG) mice does not exhibit a sex-bias pattern of lung metastasis formation (P=0.9746). However, sex bias was observed when we used CB17-SCID mice. This data suggest that innate immunity is partly responsible for the sex bias of LKB1-mutant lung cancer formation. We also characterized immune cells from the lung with LKB1-mutant tumors. Monocytes/macrophages decreased from 23% to 19%, and neutrophils increased from 15% to 19%. Lymphoid cells remained the same at 58%, and T-cells account for 34% of all CD45+ cells. Interestingly, T-cells doubled to account for 81% of all CD45+ cells from the lung in female mice resistant to the formation of lung metastasis. Our data indicated that both the innate and the adaptive immunity are responsible for eliminating LKB1-mutant lung adenocarcinoma in female mice. Citation Format: Yijian Fan, Lenore Monterroza, Rui Jin, Xiuju Liu, Periasamy Selvaraj, Rabindra Tirouvanziam, Wei Zhou. The role of innate and adaptive immunity in the sex bias of LKB1-mutant lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 16.