Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis - PubMed (original) (raw)
. 2018 Jul;24(7):986-993.
doi: 10.1038/s41591-018-0078-7. Epub 2018 Jun 25.
Balaji Virassamy 1, Chengzhong Ye 3 4 5, Agus Salim 3 6, Christopher P Mintoff 1, Franco Caramia 1, Roberto Salgado 1 7, David J Byrne 8, Zhi L Teo 1 2, Sathana Dushyanthen 1, Ann Byrne 1, Lironne Wein 1, Stephen J Luen 1, Catherine Poliness 9, Sophie S Nightingale 9, Anita S Skandarajah 9 10, David E Gyorki 9, Chantel M Thornton 9, Paul A Beavis 1 2, Stephen B Fox 2 8; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab); Phillip K Darcy 1 2, Terence P Speed 3 11, Laura K Mackay 12, Paul J Neeson 13 14, Sherene Loi 15 16
Affiliations
- PMID: 29942092
- DOI: 10.1038/s41591-018-0078-7
Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis
Peter Savas et al. Nat Med. 2018 Jul.
Erratum in
- Publisher Correction: Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis.
Savas P, Virassamy B, Ye C, Salim A, Mintoff CP, Caramia F, Salgado R, Byrne DJ, Teo ZL, Dushyanthen S, Byrne A, Wein L, Luen SJ, Poliness C, Nightingale SS, Skandarajah AS, Gyorki DE, Thornton CM, Beavis PA, Fox SB; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab); Darcy PK, Speed TP, Mackay LK, Neeson PJ, Loi S. Savas P, et al. Nat Med. 2018 Dec;24(12):1941. doi: 10.1038/s41591-018-0176-6. Nat Med. 2018. PMID: 30135555
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 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.
Comment in
- Sequencing cells of the immune TME.
Killock D. Killock D. Nat Rev Clin Oncol. 2018 Sep;15(9):531. doi: 10.1038/s41571-018-0069-0. Nat Rev Clin Oncol. 2018. PMID: 29985469 No abstract available. - Resident Breast T Cells: The Troops Are Already There.
Schalck A, Bernatchez C, Navin N. Schalck A, et al. Trends Mol Med. 2018 Oct;24(10):821-822. doi: 10.1016/j.molmed.2018.07.006. Epub 2018 Aug 1. Trends Mol Med. 2018. PMID: 30077643 Free PMC article.
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