TY - JOUR AU - Egelston, Colt A. AU - Avalos, Christian AU - Tu, Travis Y. AU - Rosario, Anthony AU - Wang, Roger AU - Solomon, Shawn AU - Srinivasan, Gayathri AU - Nelson, Michael S. AU - Huang, Yinghui AU - Lim, Min Hui AU - Simons, Diana L. AU - He, Ting-Fang AU - Yim, John H. AU - Kruper, Laura AU - Mortimer, Joanne AU - Yost, Susan AU - Guo, Weihua AU - Ruel, Christopher AU - Frankel, Paul H. AU - Yuan, Yuan AU - Lee, Peter P. T1 - Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients PY - 2019/10/03/ AB - CD8+ tumor-infiltrating lymphocytes (TILs) correlate with relapse-free survival (RFS) in most cancer types, including breast cancer. However, subset composition, functional status, and spatial location of CD8+ TILs in relation to RFS in human breast tumors remain unclear. Spatial tissue analysis via quantitative immunofluorescence showed that infiltration of CD8+ T cells into cancer islands was more significantly associated with RFS than CD8+ T cell infiltration into either tumor stroma or total tumor. Localization into cancer islands within tumors is mediated by expression of the integrin CD103, which is a marker for tissue-resident memory T cells (TRMs). Analysis of fresh tumor samples revealed that CD8+ TRMs are functionally similar to other CD8+ TILs, suggesting that the basis of their protective effect is their spatial distribution rather than functional differences. Indeed, CD103+ TRMs, as compared with CD103–CD8+ TILs, are enriched within cancer islands, and CD8+ TRM proximity to cancer cells drives the association of CD8+ TIL densities with RFS. Together, these findings reveal the importance of cancer island–localized CD8+ TRMs in surveillance of the breast tumor microenvironment and as a critical determinant of RFS in patients with breast cancer. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.130000 VL - 4 IS - 19 UR - https://doi.org/10.1172/jci.insight.130000 PB - The American Society for Clinical Investigation ER -