The T cell senescence in breast cancer

Abstract

Background: The cancer-immune cell crosstalk is a common immune-evasion mechanism of cancer. This crosstalk can result in epigenetic changes in immune phenotypes to accelerate tumor growth and metastasis. Senescent T lymphocytes are formed during T cell differentiation, and are recently described as one of the dysfunctional T cells in cancer. In breast cancer, estrogen does not only regulate normal physiology in females, but is also involved in cancer development and cancer treatment. It may also attenuate senescent phenotypes, and increase DNA damage in several cell-lines. This thesis therefore examined for the presence of senescent T lymphocytes in breast cancer patients, the effects of breast cancer on epigenetic changes in circulating immune cells, and the effects of estrogen hormones on senescent T lymphocytes.

Methods: The in-vitro co-culture of cancer sera and normal leukocytes were examined for the methylation level by COBRA Alu technique. Senescent T cells were examined for β-galactosidase, CD28, and CD57 in breast cancer patients by flow cytometry technique. In addition, cellular senescence models were created by adding etoposide. Addition of estrogen hormones were performed in cellular senescence models, and DNA damage markers, including phospho-γH2AX, p53, and p21 were examined by flow cytometry. The statistical significance was considered as p-value < 0.05. The analysis was performed using IBM SPSS software.

Results: The breast cancer serum was found to epigenetically modify to normal leukocytes. The aging-associated epigenetic changes were correlated with cancer prognosis. In clinical samples, the non-exhausted senescent phenotypes were correlated with the progression of age, and the increase in these phenotypes was found in breast cancer patients. Moreover, these senescent phenotypes were prematurely presented in breast cancer patients. In cellular senescence models, the supplement of estrogen improved senescent phenotypes, and seemed to have DNA damage attenuation effects.