Abstract
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.
Highlights
Childhood maltreatment, such as abuse and neglect, increases the vulnerability for the development of psychiatric disorders and cancer in adult life [1, 2]
We investigated the presence of immunosenescence markers in women newly diagnosed with breast cancer with and without history of childhood maltreatment
Individuals of CM+ and CM− groups differed from control group by age, years of education, and income
Summary
Childhood maltreatment, such as abuse and neglect, increases the vulnerability for the development of psychiatric disorders and cancer in adult life [1, 2]. Life Stress and Breast Cancer with important psychological burden and can be understood as a “second allostatic hit” [6], further activating the stress system [7]. This profile is associated with dysregulation of the immune system, mainly characterized by increased levels of proinflammatory cytokines and early senescence [8,9,10,11]. The understanding of biological changes associated with early life stress at the cancer onset is of paramount importance The monitoring of these biomarkers would be beneficial for planning therapies and optimizing the timing of treatment
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