Background and Objective: Breast cancer is one of the most common diseases worldwide and the second leading cause of death among women. Immune responses play a critical role in inhibiting the onset and progression of this disease. Given the important role of T lymphocytes in identifying and preventing the spread of breast cancer tumor cells, this study was conducted to simultaneously evaluate the regulatory molecules CXC chemokine receptor 3 (CXCR3), programmed cell death protein 1 (PD-1), natural killer group 2 member D (NKG2D), and transforming growth factor beta 1 receptor II (TGF-βRII) on T lymphocytes of newly diagnosed breast cancer patients.
Methods: This case-control study was performed on 26 newly diagnosed breast cancer patients (mean age = 46.2±9.5 years) admitted to the Fifth Azar Educational-Therapeutic Center in Gorgan, Iran, and 12 non-breast cancer individuals (mean age = 42.9±9.9 years) selected from the staff and students of Golestan University of Medical Sciences during 2018-2019. First, blood sampling was performed and peripheral blood mononuclear cells (PBMCs) were isolated. Then, using flow cytometry, different cell populations were evaluated for the expression of CXCR3, PD-1, NKG2D, and TGF-βRII. Plasma levels of interferon gamma (IFN-γ) and major histocompatibility complex class I chain related gene-A (MIC-A) were measured by enzyme-linked immunosorbent assay (ELISA).
Results: The mean percentage of T lymphocyte population in newly diagnosed breast cancer patients was significantly lower compared to healthy individuals (P<0.05). Also, the mean percentage of T lymphocytes expressing PD-1 and TGF-βRII was higher in the case group compared to the control group, while the expression of NKG2D and CXCR3 showed lower levels (P<0.05). The results of comparing plasma concentrations of IFN-γ and MIC-A indicated that the case group had higher levels of MIC-A than the control group (P<0.05); however, no statistically significant difference was found regarding IFN-γ.
Conclusion: It seems that the increased expression of TGF-βRII and PD-1 along with the decreased expression of NKG2D and CXCR3 and the reduced level of MIC-A in newly diagnosed breast cancer patients may be related to upregulation and potent suppression of T lymphocyte immunity and their dysfunction in breast cancer disease.