Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients
Colt A. Egelston, … , Yuan Yuan, Peter P. Lee
Colt A. Egelston, … , Yuan Yuan, Peter P. Lee
Published October 3, 2019; First published August 29, 2019
Citation Information: JCI Insight. 2019;4(19):e130000. https://doi.org/10.1172/jci.insight.130000.
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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

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Figure 1

CD103+CD8+ T cells localize to epithelial cell regions in breast tumors and non-cancerous breast tissues.

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CD103+CD8+ T cells localize to epithelial cell regions in breast tumors ...
(A) Formalin-fixed, paraffin-embedded (FFPE) tissues were assayed for expression of CD103 on CD8+ T cells by quantitative immunofluorescence (QIF). Whole-tissue sections from breast tumors or noncancerous breast tissues (NCBTs) were stained and imaged, followed by quantitative analysis of representative fields. Pan-cytokeratin (CK; shown in gray), CD8 (shown in cyan), and CD103 (shown in red) stains are depicted as composite images. Tissue segmentation algorithms based on CK staining allowed for distinct identification of cancer islands and stroma areas or epithelial ducts and stroma areas in tumors and NCBTs, respectively. T cell phenotypes (cyan dots, CD8+CD103–; red dots, CD8+CD103+) were created as shown for quantification and localization within segmented tissues. Scale bars: 50 μm. (B) Total CD8+ T cell density in either cancer islands or stroma was assessed. The percentages of CD8+ T cells expressing CD103 within segmented areas of breast tumors (C) and NCBTs (D) were assessed. Each symbol represents data from a unique patient sample. Tumor samples n = 25. NCBT samples n = 8. Significance was calculated using 2-tailed Student’s t tests. ****P < 0.0001.