Context-dependent role of Treg-derived IL-10 in shaping tumor immunity 3527

Abstract Description Regulatory T cells (Tregs) play a dual role in tumor progression, traditionally associated with suppression of anti-tumor immunity yet potentially protective against tumor-promoting inflammation. Among their mediators, IL-10 exhibits pleiotropic effects in cancer, demonstrating both tumor-promoting and inhibiting functions. In this study, we investigated the role of Treg-derived IL-10 across diverse tumor types and tissue environments. To address this, we generated mice with conditional IL-10 deletion in Foxp3+ Tregs and assessed the impact of temporal IL-10 deficiency in Tregs in NSCLC lung and colorectal carcinoma (CRC) models. Strikingly, we found opposing roles for Treg-derived IL-10 across tumor types. In NSCLC, IL-10 deficiency in Tregs led to increased tumor growth as well as a reduction in cytotoxic T cell number and activation levels. In contrast, loss of Treg IL-10 resulted in reduced tumor burden in syngeneic and inflammation-driven CRC models. By analyzing the cellular composition and signaling networks within the tumor microenvironment, using high throughput flow cytometry and single-cell sequencing, we aim to further elucidate the distinct regulatory patterns of Treg-derived IL-10 in the tumors. Our findings propose a dual, context-dependent role of Treg-derived IL-10 in shaping tumor immunity and potentially illuminating an environment-specific immune modulation, with implications for therapeutic strategies accounting for tumor type and ontogeny. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)