Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients

CA Egelston, C Avalos, TY Tu, A Rosario, R Wang… - JCI …, 2019 - pmc.ncbi.nlm.nih.gov
CA Egelston, C Avalos, TY Tu, A Rosario, R Wang, S Solomon, G Srinivasan, MS Nelson
JCI insight, 2019pmc.ncbi.nlm.nih.gov
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 …
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.
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