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.
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
Title and authors | Publication | Year |
---|---|---|
TCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals
F Manfredi, BC Cianciotti, A Potenza, E Tassi, M Noviello, A Biondi, F Ciceri, C Bonini, E Ruggiero |
Frontiers in immunology | 2020 |
Breast Cancer Heterogeneity and Response to Novel Therapeutics
M Baliu-Piqué, A Pandiella, A Ocana |
Cancers | 2020 |
Memory CD8+ T cell responses to cancer
J Han, N Khatwani, TG Searles, MJ Turk, CV Angeles |
Seminars in Immunology | 2020 |
Tissue-resident memory-like T cells in tumor immunity: Clinical implications
MV Dhodapkar, KM Dhodapkar |
Seminars in Immunology | 2020 |
Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types
JK Khalsa, N Cheng, J Keegan, A Chaudry, J Driver, WL Bi, J Lederer, K Shah |
Nature Communications | 2020 |
Resident Memory T Cells and Their Effect on Cancer
DJ Craig, JF Creeden, KR Einloth, CE Gillman, L Stanbery, D Hamouda, G Edelman, L Dworkin, JJ Nemunaitis |
Human vaccines | 2020 |
Racial differences in CD8+ T cell infiltration in breast tumors from Black and White women
Y Abdou, K Attwood, TY Cheng, S Yao, EV Bandera, GR Zirpoli, RP Ondracek, L Stein, W Bshara, T Khoury, CB Ambrosone, AR Omilian |
Breast Cancer Research | 2020 |
The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer
SL Goff, DN Danforth |
Clinical Breast Cancer | 2020 |