Tumor-specific CD8 T cell characterization in HR+ breast cancer reveals an impaired antitumoral response in patients with lymph node metastasis.
Pinho MP., Antoun E., Sandhar B., Shu T., Gao F., Yang X., Bates A., Cerundolo L., Hamid MHBA., Maldonado-Perez D., Teague R., Warner E., Winter L., Alham NK., Verrill C., Lord SR., Rostron T., Clark S-A., Waugh C., Sopp P., Conlon C., Fernandes RA., Harris AL., Peng Y., Adwani A., Dong T.
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.