Multi-epitopic anti-tumor T cell responses and efficient Trastuzumab-mediated ADCC promote a favorable clinical outcome in HER2+ breast cancer patients after neoadjuvant chemotherapy (165.8)

Abstract The ability of drugs such as Trastuzumab and taxanes to act through immunomediated and/or immunomodulatory mechanisms suggest that anti-tumor immune responses may influence the clinical outcome of breast cancer patients. We have enumerated circulating CD8+ T cells specific for a broad spectrum of tumor-associated antigens (her2, muc-1, mammaglobin-A, trag-3, survivin, bcl-xL) in 13 patients with locally advanced breast cancer (6 HER2+ and 7 HER2-). At diagnosis, increased numbers of CD8+ T cells specific for all 13 HLA-A*0201 epitopes were observed in the whole series, with a markedly higher extent in HER2+ cases. This subset of patients retained an immunological profile similar to that of healthy women, whereas HER2- cases showed decreased circulating CD3+ T lymphocytes, higher numbers of regulatory T cells and alterations in serum cytokine levels (decreased IL-2, IL-6, and IL-8). Notably, patients with complete pathologic response (pCR), unlike those showing partial responses, retained high numbers of epitope-specific CD8+ T cells throughout the neoadjuvant chemotherapy (NC) treatment, particularly versus survivin and mammaglobin-A epitopes. Moreover, a higher efficacy of Trastuzumab-mediated ADCC in vitro correlated with the induction of pCR in HER2+ cases. These findings emphasize the crucial role of host anti-tumor T cell responses in promoting a favourable clinical outcome in the setting of neoadjuvant chemotherapy for breast cancer, particularly in HER2+ cases.