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

Virassamy, B; Caramia, F; Savas, P; Sant, S; Wang, J; Christo, SN; Byrne, A; ... Loi, S; + view all (2023) Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer. Cancer Cell , 41 (3) 585-601.e8. 10.1016/j.ccell.2023.01.004. Green open access

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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-CTLA-4 therapy resulted in expansion of these intratumoral populations, with the TRM-like subset displaying significantly enhanced cytotoxic capacity. TRM-like CD8+ T cells could also provide local immune protection against tumor rechallenge and a TRM gene signature extracted from tumor-free tissue was significantly associated with improved clinical outcomes in TNBC patients treated with checkpoint inhibitors.

Type: Article
Title: Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ccell.2023.01.004
Publisher version: https://doi.org/10.1016/j.ccell.2023.01.004
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Keywords: Triple-negative breast cancer, tumor infiltrating lymphocytes, tissue-resident memory cells, intratumoral CD8+ T cells, cancer immunotherapy, immune checkpoint blockade, CTLA-4, PD-1, tumor immunity, cancer immune surveillance
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10213384
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