Abstract 1339: Interleukin 4 Producing CD4 T cells initiate a crucial event for lung cancer development

Lung cancer remains one of the leading causes of mortality of cancer patients. Kinase-dead Ikkα knock-in (KA/KA) mice develop CD4 T cell-derived autoimmune disease. Previously, we reported spontaneous lung squamous cell carcinoma (SCC) associated with increase macrophage and CD4 T cell numbers in KA/KA mice. Depleting macrophages dampens lung SCC development in KA/KA mice, but a lot of CD4 T cells remain in the lungs. The activity of CD4 T cells in lung SCC development is unknown. In this study, we attempted to investigate the role of CD4 T cells in lung SCC development. We performed adoptive CD4 T cell transfer experiment and found that KA/KA CD4 T cell transfer, not WT CD4 T cells, recruited marked macrophages to the lungs and induced lung SCC in KA/KA;Rag1-/- mice. The CD4 T cells isolated from the lungs of KA/KA mice and KA/KA;Rag1-/- mice with KA/KA CD4 T cell transfer expressed elevated PD-1, IL-4, IL-5, Il-13, and Il-21 levels compared to WT mice. We found that Il4 ablation, not Il5 deletion, reduced macrophage recruitment and blocked SCC development in KA/KA;Il4-/- mice as well as unlike KA/KA CD4 T cells, KA/KA;Il4-/- CD4 T cells did not induce spontaneous lung SCC in KA/KA;Rag1-/- mice with KA/KA;Il4-/- CD4 T cell injections. Taken together, the finding highlights a pathogenic role of IL-4-producing CD4 T cells in lung carcinogenesis. Citation Format: Gajendra Jogdand, Sayantan Banerjee, Gongping Shi, Jami Willet Brown, Amit Singh, Yongmei Zhao, Jyoti Shetty, Bao Tran, Yinling Hu. Interleukin 4 Producing CD4 T cells initiate a crucial event for lung cancer development [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 1339.