Tip-1 Yardımcı T (Th1) Hücrelerin Radyasyon Stresi Altında Fonksiyonel ve Fenotipik Değişimlerinin İncelenmesi

Abstract

It's critical to understand changes in the functional and phenotypic status of T cells, which play a key role in the anti-tumor response due to the immunosuppressive environment in the tumor microenvironment. In chronic inflammation such as cancer, T cells can differentiate into dysfunctional exhausted phenotype cells and express high inhibitory receptors. Effector functions of exhausted T cells can be restored with the help of blockade of inhibitory receptors. On the other hand, a combination of radiotherapy and blockade therapy is predicted to enhance anti-tumor immune responses. Within the scope of this in vitro thesis study, THR signal was provided by an anti-CD3 monoclonal antibody and co-stimulation was provided by a monocytic cell line, resulting in continual stimulation of CD4+ helper T cells. Functional and phenotypic changes of T cells of different phenotypes under radiation stress at different doses (0 Gy, 2 Gy, 5 Gy, 8 Gy, and 12 Gy) were investigated at different incubation times (0, 24, 72, and 120 hours) of the co-culture model used. After differentiating into effector cells that produce IL-2, IFN-γ, and TNF-α in response to stimulation, naive CD4+ T lymphocytes become fatigued memory-like T cells that express high levels of inhibitory receptors and have decreased cytokine production. By calculating the apoptotic level and DNA break numbers, it was found that the stimulation period when cells were most radiosensitive was 72 hours, and the most sensitive subgroups were effector T lymphocytes and effector memory-like T lymphocytes. The most radiation-resistant subtypes were naive T and central memory-like T lymphocytes. It was observed that radiation did not change the mitochondrial membrane potential in Th cells. It was shown that anti-PD-1 blockade applied before radiation exposure had no negative impact on Th1 survival. As a result, it was determined that Th1 cells did not show radiation sensitivity in the process of regaining function with PD-1 blockade.