Resident memory T cells in tumor-distant tissues fortify against metastasis formation.
Journal Article (Journal Article)
As a critical machinery for rapid pathogen removal, resident memory T cells (TRMs) are locally generated after the initial encounter. However, their development accompanying tumorigenesis remains elusive. Using a murine breast cancer model, we show that TRMs develop in the tumor, the contralateral mammary mucosa, and the pre-metastatic lung. Single-cell RNA sequencing of TRMs reveals two phenotypically distinct populations representing their active versus quiescent phases. These TRMs in different tissue compartments share the same TCR clonotypes and transcriptomes with a subset of intratumoral effector/effector memory T cells (TEff/EMs), indicating their developmental ontogeny. Furthermore, CXCL16 is highly produced by tumor cells and CXCR6- TEff/EMs are the major subset preferentially egressing the tumor to form distant TRMs. Functionally, releasing CXCR6 retention in the primary tumor amplifies tumor-derived TRMs in the lung and leads to superior protection against metastases. This immunologic fortification suggests a potential strategy to prevent metastasis in clinical oncology.
- Christian, LS; Wang, L; Lim, B; Deng, D; Wu, H; Wang, X-F; Li, Q-J
- May 11, 2021
Volume / Issue
- 35 / 6
Start / End Page
- 109118 -
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States