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

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.