Features of Immunosenescence in Women Newly Diagnosed With Breast Cancer

Frontiers in Immunology

Lucas Poitevin Bandinelli¹  Rodrigo Grassi-Oliveira²  Lauren Trintinaglia³  Jaqueline Bohrer Schuch³  Marcelo Anzolin⁴  Laura Esteves Petersen⁴  Bruna Luz Correa⁵  Moisés Evandro Bauer⁶ 

[1] Centro Universitário Ritter dos Reis, Porto Alegre, Brazil;Developmental Cognitive Neuroscience Laboratory (DCNL), School of Health Sciences, Porto Alegre, Brazil;Graduate Program in Biomedical Gerontology, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil;Laboratory of Immunosenescence, School of Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil;Labvitrus Laboratory, Porto Alegre, Brazil;National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil;

关键词: childhood maltreatment;    breast cancer;    immunosenescence;    cytomegalovirus;    T lymphocytes;   

DOI  :  10.3389/fimmu.2018.01651

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown