Association between higher KI67 and higher proportion of effector T CD8 lymphocytes in HER2+ Breast Cancer patients

Ayelén Ivana Pesce Viglietti¹, María Belén Bordignon¹, Alexis Ostinelli², Florencia Perazzo³, Manglio Miguel Rizzo⁴, Federico Coló², Gabriel Crimi³, Ignacio Mc Lean4, Pablo Mandó³, Estrella Mariel Levy¹, Victoria Costanzo², Sergio Rivero²



HER-2-amplified (HER2+) breast cancer (BC) is characterized by the high expression of genes related to human epidermal growth factor receptor 2 (ERBB2/HER2). HER2+ BC patients are treated with neoadjuvant (NA) chemotherapy including anti-Her2 antibodies, trastuzumab (TRZ), and pertuzumab (PER). Considering that the adaptive immune profile in patients with HER2+ BC undergoing NA therapy could have an impact on the response to treatment, in order to find predictive markers of the response, we characterized different subpopulations of peripheral blood T lymphocytes of these patients. We analyzed by FACS T lymphocyte subpopulations that displayed markers related to exhaustion, activation, and memory from PBMC of 49 patients diagnosed before TRZ+PER therapy, and 23 healthy donors (HD). We also evaluated the association between immunological markers and clinical variables. The patients who presented a high tumor cell proliferation marker (Ki67>20), associated with chemotherapy response, showed differences in memory populations compared with those patients with a Ki67<20 and HD. In patients with KI67 >20, a lower proportion of CD8 + CM T cells (central memory) was observed (p = 0.0028; 0.047) and a greater proportion of effector CD8 + T cells (p = 0.0357; 0.023), supporting the role of immunotherapy in treating a subset of HER2+ BC. The role of T cell memory subsets predictors of response to neoadjuvant chemotherapy in HER2+ BC should be further evaluated.