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

Peter Savas; Balaji Virassamy; Chengzhong Ye; Agus Salim; Christopher P Mintoff; Franco Caramia; Roberto Salgado; David J Byrne; Zhi L Teo; Sathana Dushyanthen; Ann Byrne; Lironne Wein; Stephen J Luen; Catherine Poliness; Sophie S Nightingale; Anita S Skandarajah; David E Gyorki; Chantel M Thornton; Paul A Beavis; Stephen B Fox; Kathleen Cuningham; Phillip K Darcy; Terence P Speed; Laura K Mackay; Paul J Neeson; Sherene Loi

Journal article

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

Peter Savas, Balaji Virassamy, Chengzhong Ye, Agus Salim, Christopher P Mintoff, Franco Caramia, Roberto Salgado, David J Byrne, Zhi L Teo, Sathana Dushyanthen, Ann Byrne, Lironne Wein, Stephen J Luen, Catherine Poliness, Sophie S Nightingale, Anita S Skandarajah, David E Gyorki, Chantel M Thornton, Paul A Beavis, Stephen B Fox Show all

NATURE MEDICINE | NATURE PUBLISHING GROUP | Published : 2018

DOI: 10.1038/s41591-018-0078-7

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 T 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 dif..

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University of Melbourne Researchers

Phillip Darcy Author The Sir Peter Maccallum Department of Oncology

Zhi Ling Teo Author The Sir Peter Maccallum Department of Oncology

Sherene Loi Author The Sir Peter Maccallum Department of Oncology

Laura Mackay Author Microbiology and Immunology

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THE KATHLEEN CUNINGHAM FOUNDATION CONSORTIUM FOR RESEARCH INTO FAMILIAL BREAST CANCER (KCONFAB)

2018 NBCF ENDOWED CHAIR PROGRAM

THE KATHLEEN CUNNINGHAM FOUNDATION CONSORTIUM FOR RESEARCH INTO FAMILIAL BREAST CANCER

Grants

Awarded by Breast Cancer Research Foundation

Awarded by NHMRC

Awarded by NBCF

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

We wish to thank H. Thorne, E. Itiiedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics and the Clinical Follow Up Study (which has received funding from the National Health and Medical Research Council of Australia (NHMRC), the National Breast Cancer Foundation (NBCF), Cancer Australia and the National Institute of Health (United States) for their contributions to this research, and the many families who contribute to kConFab. We wish to thank the FACS core facility staff R. Rossi, Milovac and S. Curcio, and T. Tan and P. Petrone for additional FAGS assistance. We also thank S. Ellis for assistance with confocal imaging, G.M. Arnau for facilitating RNA-seq, and the Anatomical Pathology staff at the Peter MacCallum Cancer Centre. Special thanks also to J, Jabbari and the Australian Genome Research Facility for making the single-cell sequencing possible.r This study was funded by the Breast Cancer Research Foundation (13CRF), NY. S.L. is supported by the Cancer Council Victoria John Colebatch Fellowship and the National Breast Cancer Foundation. P.S. is supported by the NHMRC and the NBCF (Post Graduate Scholarship 1094388), the Cancer Therapeutics CRC and the Peter Mac Foundation. Z.L.T. is supported by the NHMRC (Early Career Fellowship 1106967). D.G. is supported by the Peter Mac Foundation. PA.& is supported by the NHMRC (Early Career Fellowship 17-005), S.J.L is supported by the University of Melbourne. &RE la supported by the NHMRC (Practitioner Fellowship 1079329). kConFab is supported by a grant from NBCF, and previously NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. P.K.D is supported by the NHMRC (Senior Research Fellowship 1136680 and Program Grant 1132373). TS. is supported by the NHMRC (Program Grant 1054618). RJ.N. is supported by the NHMRC (Program Grant 1132373).