par Metoikidou, Christina;Karnaukhov, Vadim;Boeckx, Bram;Timperi, Eleonora;Bonté, Pierre Emmanuel;Wang, Ling;Espenel, Marion;Albaud, Benoit;Loirat, Delphine;Wang, Xiaoxiao;Sotiriou, Christos
;Aftimos, Philippe
;Punie, Kevin;Wildiers, Hans;Labroska, Viktorija;Wang, Ming-Wei;Waterfall, Joshua J.J.;Piccart-Gebhart, Martine
;Mora, Thierry;Walczak, Aleksandra;Lantz, Olivier;Buisseret, Laurence
;Lambrechts, Diether;Amigorena, Sebastian
;Romano, Emanuela
Référence Cell Reports Medicine, 6, 3, page (101973)
Publication Publié, 2025-03





Référence Cell Reports Medicine, 6, 3, page (101973)
Publication Publié, 2025-03
Article révisé par les pairs
Résumé : | 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+ T cells in responder (R) patients. On treatment, R display an influx of newly emerging clonotypes, as well as expansion of the CD8+ 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. |