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Nat Med. 2018 Jul;24(7):986-993. doi: 10.1038/s41591-018-0078-7. Epub 2018 Jun 25.

Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis.

Author information

1
Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.
2
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
3
Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
4
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
5
School of Medicine, Tsinghua University, Beijing, China.
6
Department of Mathematics and Statistics, La Trobe University, Melbourne, Victoria, Australia.
7
Department of Pathology, GZA Ziekenhuizen, Antwerp, Belgium.
8
Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
9
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
10
Department of Surgery Royal Melbourne Hospital and Royal Womens' Hospital, University of Melbourne, Melbourne, Victoria, Australia.
11
Department of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia.
12
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
13
Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia. paul.neeson@petermac.org.
14
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. paul.neeson@petermac.org.
15
Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia. sherene.loi@petermac.org.
16
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. sherene.loi@petermac.org.

Abstract

The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient survival, particularly in triple-negative and HER2-overexpressing BC subtypes1. Although T cells are the predominant TIL population2, the relationship between quantitative and qualitative differences in T cell subpopulations and patient prognosis remains unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6,311‚ÄČT cells isolated from human BCs and show that significant heterogeneity exists in the infiltrating T cell population. We demonstrate that BCs with a high number of TILs contained CD8+ T cells with features of tissue-resident memory T (TRM) cell differentiation and that these CD8+ TRM cells expressed high levels of immune checkpoint molecules and effector proteins. A CD8+ TRM gene signature developed from the scRNA-seq data was significantly associated with improved patient survival in early-stage triple-negative breast cancer (TNBC) and provided better prognostication than CD8 expression alone. Our data suggest that CD8+ TRM cells contribute to BC immunosurveillance and are the key targets of modulation by immune checkpoint inhibition. Further understanding of the development, maintenance and regulation of TRM cells will be crucial for successful immunotherapeutic development in BC.

PMID:
29942092
DOI:
10.1038/s41591-018-0078-7

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