Cell reports. Medicine · 2025
Tumor-specific CD8 T cell characterization in HR+ breast cancer reveals an impaired antitumoral response in patients with lymph node metastasis.
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Pinho Mariana Pereira, Antoun Elie, Sandhar Balraj, Shu Ting, Gao Fei, Yang Xiaobao, Bates Adam, Cerundolo Lucia, Hamid Megat H B A, Maldonado-Perez David, Teague Renuka, Warner Eve, Winter Lucinda, Alham Nasullah Khalid, Verrill Clare, Lord Simon R, Rostron Timothy, Clark Sally-Ann, Waugh Craig, Sopp Paul, Conlon Chris, Fernandes Ricardo A, Harris Adrian L, Peng Yanchun, Adwani Asha, Dong Tao
Аннотация
Most breast cancers express the estrogen receptor (ER), but the immune response of hormone receptor-positive (HR+) breast cancer remains poorly characterized. Here, dendritic cells loaded with tumor lysate are used to identify tumor-reactive CD8 T cells, which are detected in most HR+ breast cancer patients, especially those with early-stage tumors. When present, the circulating antitumor CD8 response contains cytotoxic T cells with diverse specificity and T cell receptor (TCR) repertoire. Additionally, patients with blood cancer-specific T cells have significantly more CD8 tumor-infiltrating lymphocytes (TILs). Moreover, tumor-reactive TCR sequences are detected in the tumor, but at a significantly lower proportion in patients with lymph node involvement. Our data suggest that HR+ breast cancer patients with lymph node metastasis lack tumor-specific CD8 T cells with capacity to infiltrate the tumor at significant levels. However, early-stage patients have a diverse antitumor CD8 response that could be harnessed to develop immunotherapeutic approaches for late-stage HR+ patients.