Intratumoral CD8 T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer

B Virassamy; F Caramia; P Savas; S Sant; J Wang; SN Christo; A Byrne; K Clarke; E Brown; ZL Teo; B von Scheidt; D Freestone; LC Gandolfo; K Weber; J Teply-Szymanski; R Li; SJ Luen; C Denkert; S Loibl; O Lucas; C Swanton; TP Speed; PK Darcy; PJ Neeson; LK Mackay; S Loi

Journal article

Intratumoral CD8 T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer

B Virassamy, F Caramia, P Savas, S Sant, J Wang, SN Christo, A Byrne, K Clarke, E Brown, ZL Teo, B von Scheidt, D Freestone, LC Gandolfo, K Weber, J Teply-Szymanski, R Li, SJ Luen, C Denkert, S Loibl, O Lucas Show all

Cancer Cell | Published : 2023

DOI: 10.1016/j.ccell.2023.01.004

Abstract

CD8+ tumor-infiltrating lymphocytes with a tissue-resident memory T (TRM) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, the relative contribution of CD8+ TRM cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancer remains unknown. Here, we show that intratumoral CD8+ T cells in murine mammary tumors transcriptionally resemble those from TNBC patients. Phenotypic and transcriptional studies established two intratumoral sub-populations: one more enriched in markers of terminal exhaustion (TEX-like) and the other with a bona fide resident phenotype (TRM-like). Treatment with anti-PD-1 and anti..

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University of Melbourne Researchers

Balaji Virassamy Author

Peter Savas Author

Susan Christo Author

Zhi Ling Teo Author

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2018 NBCF ENDOWED CHAIR PROGRAM

Grants

Awarded by Breast Cancer Research Foundation

Funding Acknowledgements

The authors acknowledge staff from the Peter MacCallum Cancer Center Flow Facility, Peter MacCallum Molecular Genomics core and Peter MacCallum Cancer Center Animal Research Platform, and the Australian genome research facility (AGRF, Melbourne) for their assistance. Graphical abstract was created with BioRender.com . We thank Jeannette Parrodi for administrative support. S.Loi. is supported by the National Breast Cancer Foundation of Australia (NBCF) (APP ID: EC-17-001) , the Breast Cancer Research Foundation, New York (BCRF (APP ID: BCRF-21-102) , and a National Health and Medical Coun-cil of Australia (NHMRC) Investigator Grant (APP ID: 1162318) . L.K.M. is supported by the Grant-In-Aid Scheme administered by Cancer Council Victoria. P.K.D. is supported by a National Health and Medical Research Council Principal Research Fellowship (APP ID: 1136680) . <STRONG>C.S. is a Royal Society Napier Research Professor (RSRP\R\210001) . C.S. is a Royal Society Napier Research Professor (RSRP\R\210001)</STRONG> . His work is supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (CC2041) , the UK Medical Research Council (CC2041) , and the Wellcome Trust (CC2041) and the Breast Cancer Research Foundation (US) BCRF-22-157. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manu-script version arising from this submission.C.D., and S.Loibl are supported by a research grant from the German Cancer Aid (Deutsche Krebshilfe, Translational Oncology, Integrate-TN project; 70113450) and European Commission H2020 (Oncobiome project; 825410) .