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.
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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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