Abstract 1892: Dysfunction of resident memory CD8+ T cells facilitates breast cancer lung metastasis

Abstract Resident memory T cells (TRM) are generally intraepithelially located and manifesting defence potential in diverse existing virus infection models. However, their roles in cancer development, especially metastasis, are poorly understood. Herein, by using a murine model orthotopically inoculated with 4T1 mammary carcinoma cells, we demonstrated the dynamic distribution and functional changes of lung TRM during the formation of lung pre-metastatic niche. Peri-alveolar accumulation of CD8+ T cells, which constitutively express early activation marker CD69 and epithelial-resident marker CD103, is identified. These draining lymph nodes originated and tumor-specific TRM cells, with high expression of IFN-γ and other cytotoxic cytokines, patrol along blood stream and infiltrate in the pre-metastatic lung. IFN-γ coverts alveolar macrophages in the pre-metastatic lung into a immunosuppressive phenotype with high expression of IDO1, which reciprocally compromises the anti-tumor effects of TRM. In conclusion, our study revealed the alteration of lung TRM during the process of metastasis and its interaction with lung pre-metastatic niche, indicating that by finding possible approaches to enhancing TRM function or strengthening local defenses could decrease breast cancer lung-tropic metastasis. Citation Format: Erwei Song, Yue Xing, Shicheng Su. Dysfunction of resident memory CD8+ T cells facilitates breast cancer lung metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1892.