Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients
Colt A. Egelston, Christian Avalos, Travis Y. Tu, Anthony Rosario, Roger Wang, Shawn Solomon, Gayathri Srinivasan, Michael S. Nelson, Yinghui Huang, Min Hui Lim, Diana L. Simons, Ting-Fang He, John H. Yim, Laura Kruper, Joanne Mortimer, Susan Yost, Weihua Guo, Christopher Ruel, Paul H. Frankel, Yuan Yuan, Peter P. Lee
Colt A. Egelston, Christian Avalos, Travis Y. Tu, Anthony Rosario, Roger Wang, Shawn Solomon, Gayathri Srinivasan, Michael S. Nelson, Yinghui Huang, Min Hui Lim, Diana L. Simons, Ting-Fang He, John H. Yim, Laura Kruper, Joanne Mortimer, Susan Yost, Weihua Guo, Christopher Ruel, Paul H. Frankel, Yuan Yuan, Peter P. Lee
View: Text | PDF
Research Article Immunology Oncology

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

Abstract

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.

Authors

Colt A. Egelston, Christian Avalos, Travis Y. Tu, Anthony Rosario, Roger Wang, Shawn Solomon, Gayathri Srinivasan, Michael S. Nelson, Yinghui Huang, Min Hui Lim, Diana L. Simons, Ting-Fang He, John H. Yim, Laura Kruper, Joanne Mortimer, Susan Yost, Weihua Guo, Christopher Ruel, Paul H. Frankel, Yuan Yuan, Peter P. Lee

×

Figure 6

Proximity of CD103+CD8+ TRMs and not CD103−CD8+ T cells to cancer cells in breast tumors associates with relapse-free outcome.

Options: View larger image (or click on image) Download as PowerPoint
Proximity of CD103+CD8+ TRMs and not CD103−CD8+ T cells to cancer cells ...
FFPE tissues of relapse or relapse-free patients were assessed for the spatial relationship between CD103+CD8+ or CD103–CD8+ and CK cancer cells. (A) Representative phenotype-mapped images with CK+ (gray), DAPI (blue), and T cell type phenotypes (cyan dots, CD103–CD8+; red dots, CD103+CD8+) are shown with white lines representing nearest neighbor analysis of T cells within 25 μm of a CK+ cancer cell as depicted in a cartoon graphic. Spatial localization of CD103+CD8+ and CD103–CD8+ T cells within 0–25 μm, 25–50 μm, 50–100 μm, or more than 100 μm of the nearest CK+ cancer cell was assessed in all tumors (B) and is shown with regard to relapse and nonrelapse groups as scatter plots (C). Each symbol represents data from a unique patient sample. Tumor samples n = 25. Significance was calculated using Holm-Šídák multiple-comparisons tests. ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001.