Features of Immunosenescence in Women Newly Diagnosed With Breast Cancer

Lauren Trintinaglia, Lucas Poitevin Bandinelli, Rodrigo Grassi-Oliveira, Laura Esteves Petersen, Marcelo Anzolin, Bruna Luz Correa, Jaqueline Bohrer Schuch, Moisés Evandro Bauer

Adults exposed to childhood maltreatment have increased stress reactivity. This profile is associated with dysregulation of the immune system, including enhanced inflammatory reactions and accelerated senescence. Subjects exposed to ear stress have increased risk for several age-related diseases, including cardiovascular disease, type II diabetes, and cancer. Although previous studies have reported immune changes in advanced cancer, very little information is available regarding early stage breast cancer. Here, 29 patients with breast cancer were recruited: 15 with history of childhood maltreatment (CM+) and 14 without history (CM-). Twenty-seven healthy women without CM were selected as the control group. Peripheral blood was collected and lymphocyte subsets phenotyped by multi-color flow cytometry (B cells, CD4+ T, CD8+ T, natural killer cells, activated T cells, regulatory T cells, and senescence-associated T cells). Because human cytomegalovirus (CMV) was associated with signatures of early senescence, the CMV serology was determined by ELISA. None of the subjects had IgM reactivity to CMV, excluding acute viral infection. There was a higher proportion of patients with increased CMV IgG levels in the CM+ group as compared to CM- or controls. Different stages of T-cell differentiation can be determined based on the cell-surface expression of the costimulatory molecules CD27 and CD28: ear (CD27+CD28+), intermediate-differentiated (CD27-CD28+), and late-differentiated or senescent T cells (CD27-CD28-). After adjusting for age and education, ear T cells (CD27+CD28+) were found reduced in CM+ and CM- patients (p < 0.0001). In contrast, intermediate-differentiated T cells (CD27-CD28+; p < 0.0001), senescent T cells (CD27-CD28-; p < 0.0001), and exhausted T cells (CD8+CD27-CD28-PD1+; p < 0.0001) were found expanded in both CM+ and CM- groups. Our data suggest that features of immunosenescence are associated with newly diagnosed breast cancer, regardless of the CM history.