Immunological modulation of the Th1/Th2 shift by ionizing radiation in tumors (Review)

Abstract

Extensive evidence has documented that the balance between cytokines from T helper type 1 (Th1) and type 2 (Th2) cells is disrupted in the tumorigenic microenvironment compared with immunocompetent individuals. Ionizing radiation (IR) has been reported to markedly modulate the Th1/Th2 polarization in a concentration-dependent manner. In the present review article, the immune modulation of Th1/Th2 and the IR-induced crosstalk of the Th1/Th2 shift with immunocytes and tumor cells are summarized. The involvement of the Th1/Th2 shift in post-radiotherapy complications is highlighted. Specifically, high-dose IR has been shown to promote the Th2 shift, leading to an immunosuppressive cytokine network, while the impact of low-dose IR remains controversial. The IR-induced modulation of the Th1/Th2 shift is mediated by tumor cells and multiple immunocytes, including dendritic cells, tumor-associated macrophages, cytotoxic T lymphocytes and natural killer cells. However, the excessive production of pro-inflammatory factors, such as IFN-γ and IL-2, by Th1 cells, aggravates the clinical side-effects of radiotherapy, including radiation-induced lung and intestinal injury, radiation encephalopathy, as well as other complications. Therefore, further research into the underlying mechanism is required to confirm the potential applicability of the Th1/Th2 shift combined with IR in the treatment of malignant tumors.