Tumor-specific CD8 T cell characterization in HR+ breast cancer reveals an impaired antitumoral response in patients with lymph node metastasis.

Abstract

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.