{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Metoikidou C"],"funding":["National League Against Cancer","European Research Council","French National Cancer Institute"],"pagination":["101973"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11970331"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(3)"],"pubmed_abstract":["Chemotherapy combined with immune checkpoint blockade has shown clinical activity in breast cancer. Response, however, occurs in only a low proportion of patients. How the immune landscape of the tumor determines the immune and clinical responses to chemoimmunotherapy is not well understood. Here, using a combination of single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq), we profile 40 biopsies from 27 patients with metastatic triple-negative breast cancer (TNBC), receiving chemotherapy and anti-PD-L1 alone or in combination with anti-CD73, in a phase 2 randomized clinical trial. Our results show an enrichment of late-dysfunctional, clonally expanded CD8<sup>+</sup> T cells in responder (R) patients. On treatment, R display an influx of newly emerging clonotypes, as well as expansion of the CD8<sup>+</sup> precursors. Collectively, our data suggest that baseline clonal expansion could be a potential predictor of response and that both clonal reinvigoration of pre-existing tumor-reactive T cells and clonal replacement on-treatment are important for a protective response to chemoimmunotherapy."],"journal":["Cell reports. Medicine"],"pubmed_title":["Continuous replenishment of the dysfunctional CD8 T cell axis is associated with response to chemoimmunotherapy in advanced breast cancer."],"pmcid":["PMC11970331"],"funding_grant_id":["101055422"],"pubmed_authors":["Piccart-Gebhart M","Buisseret L","Wang MW","Sotiriou C","Wildiers H","Lantz O","Aftimos P","Walczak A","Wang L","Mora T","Waterfall JJ","Wang X","Bonte PE","Punie K","Romano E","Metoikidou C","Loirat D","Albaud B","Labroska V","Lambrechts D","Timperi E","Espenel M","Boeckx B","Karnaukhov V","Amigorena S"],"additional_accession":[]},"is_claimable":false,"name":"Continuous replenishment of the dysfunctional CD8 T cell axis is associated with response to chemoimmunotherapy in advanced breast cancer.","description":"Chemotherapy combined with immune checkpoint blockade has shown clinical activity in breast cancer. Response, however, occurs in only a low proportion of patients. How the immune landscape of the tumor determines the immune and clinical responses to chemoimmunotherapy is not well understood. Here, using a combination of single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq), we profile 40 biopsies from 27 patients with metastatic triple-negative breast cancer (TNBC), receiving chemotherapy and anti-PD-L1 alone or in combination with anti-CD73, in a phase 2 randomized clinical trial. Our results show an enrichment of late-dysfunctional, clonally expanded CD8<sup>+</sup> T cells in responder (R) patients. On treatment, R display an influx of newly emerging clonotypes, as well as expansion of the CD8<sup>+</sup> precursors. Collectively, our data suggest that baseline clonal expansion could be a potential predictor of response and that both clonal reinvigoration of pre-existing tumor-reactive T cells and clonal replacement on-treatment are important for a protective response to chemoimmunotherapy.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-01T23:15:33.666Z","creation":"2026-05-23T03:08:02.794Z"},"accession":"S-EPMC11970331","cross_references":{"pubmed":["39983715"],"doi":["10.1016/j.xcrm.2025.101973"]}}