Tumor-specific CD8 T cells in a primary human breast carcinoma : a detailed analysis

The clinical efficacy of immunostimulatory antibodies targeting the PD-1 pathway in cancer is likely mediated by CD8 T cells recognizing tumor-specific antigens. Whether breast carcinomas (BCs) are infiltrated by such cells is not known. We wished to obtain evidence for the presence of tumor-specific CD8 T cells in primary BCs. Random sets of CD8 T cell clones were derived from 6 BCs that we screened for recognition of candidate tumor-specific antigenic peptides, which were encoded either by mutated genes or by cancer-germline genes. One of these sets contained 6 different clones that recognized 4 mutant peptides, thus demonstrating that some primary BCs are immunogenic. The corresponding tumor displayed a DNA mismatch repair deficiency associated with a high number of mutations compared to the other 5 tumors. In these 5 tumors, the estimated number of presented mutant antigenic peptides was very low or zero, likely explaining the absence of detectable tumor-specific T cells.