Regulatory and effector T cell subsets and dendritic cells in breast cancer

Abstract

9697 Background: Successful immune responses against breast cancer may depend on the balance between immune stimulation mediated through dendritic cells (DC) & cytolytic T cells, and immune inhibition mediated in part by CD4+CD25+ regulatory T cells (Treg) and CTLA4 expression on T cells. We hypothesized that low anti-tumor immunity in breast cancer patients might be partially explained by aberrations in the frequencies of these different components of the immune response compared with healthy individuals. Methods: We analyzed whole blood from 26 breast cancer patients (9 stage I, 8 stage II, 3 stage III, 6 stage IV) for Treg, DC subsets, CD8+CD45RA+CCR7- cytolytic effectors, and CTLA4 expressing T cells. Controls were 41 healthy volunteers. Results: Breast cancer patients overall had higher levels of Treg (37+/−14% of CD4+ T cells) than controls (26.3 +/− 9%; p=0.002). Treg were higher in patients with stage II-IV disease, positive lymph nodes, and age < 65. Patients <65 also tended to have higher levels of CTLA4 on both CD4 and CD8+ T cells. Across all patients, there was a high positive correlation (0.82) of CTLA4 expression on Treg and CD8+ T cells, suggesting that the presence of this suppressive molecule may be a more generalized phenomenon in some individuals. The only groups that differed in CD8+CD45RA+CCR7- cytolytic effectors were premenopausal patients who had lower levels than post-menopausal women (37 vs 54%, p=0.04). Across all the patients, there was a modest negative correlation (−0.44) between Treg and CD8+ CD45RA+CCR7- suggesting that Treg may inhibit development of cytotoxic effector T cells. Finally, patients receiving chemotherapy and those with Stage IV disease had lower levels of immunostimulatory CD11c+ DC and higher levels of immunomodulatory CD123+ DC than other patients suggesting a possible negative impact of chemotherapy and advanced disease on stimulatory DC. Conclusions: This data highlights the inhibitory environment of the immune system in breast cancer patients, particularly those with advanced disease and younger age. Modification of this inhibitory environment will be needed to increase the activity of immunotherapy interventions in these patients. No significant financial relationships to disclose.