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.
Journal article
2025-08-19T00:00:00+00:00
6
CDR3, CTA, ER+ breast cancer, T cell receptor, T cell repertoire, antitumor CD8 T cells, cancer testis antigen, metastatic luminal breast cancer, moDC, tumor lysate, tumor-specific T cells, Humans, Breast Neoplasms, Female, CD8-Positive T-Lymphocytes, Lymphatic Metastasis, Lymphocytes, Tumor-Infiltrating, Receptors, Estrogen, Middle Aged, Receptors, Antigen, T-Cell, Dendritic Cells, Lymph Nodes