Radiation-Induced Immune Modulation and Inflammatory Responses in Human Cells and Tissues

Radiation exposure from environmental sources, medical procedures, or space exploration poses considerable risks to human health, with profound effects on immune function and inflammatory responses. Radiotherapy (RT) is a cornerstone of modern cancer treatment, leveraging ionizing radiation to induce DNA damage and tumor cell death. However, its biological effects extend beyond direct cytotoxicity, exerting complex and context-dependent influences on both innate and adaptive immunity. Ionizing radiation can enhance antitumor immune responses by promoting tumor antigen release, activating dendritic cells, and augmenting cytotoxic T-cell priming. Conversely, it can also induce immunosuppressive mechanisms, including lymphocyte depletion, regulatory T-cell expansion, immune checkpoint upregulation, and chronic inflammatory signaling, which may limit therapeutic efficacy. These immune effects are critical for optimizing RT protocols, particularly in the era of immunotherapy, where immune modulation plays a pivotal role in treatment efficacy. This review summarizes the current knowledge concerning how radiation induces immune and inflammatory responses in cells and tissues; focuses on key molecular pathways such as the DNA damage response, cGAS–STING signaling, and immune checkpoint modulation; and discusses their clinical implications. These findings provide potential therapeutic strategies for cancer treatment by harnessing the immunomodulatory potential of radiation while reducing adverse effects and for the prevention and treatment of radiation-related diseases.