Abstract

Cancer immunology largely depends on the effects of radiation therapy (RT). RT is predominantly focused on inducing tumor cell death, triggering anti-tumor immune responses, and generating DNA damage. Although the immune system has the ability to recognize and reject specific tumors, some tumors acquire characteristics that allow them to evade immune destruction by expressing a highly immunosuppressive microenvironment and decreasing their immunogenicity. Exposing the tumor site to radiation stimulates tumor-specific antigens, making them perceptible to the immune system and stimulating the priming and activation of cytotoxic T cells. In addition, tissue damage caused by radiation applied to the tumor microenvironment moderates a release of inflammatory cytokines that assists in leukocyte infiltration to the damage site and promotes an adaptive immune response. Furthermore, RT can reinforce tumor cell susceptibility to T cells, enhancing their eradication and apoptosis. Cancer cell apoptosis can manifest in the form of immunogenic cell death (ICD) or non-immunogenic cell death (non-ICD). While non-immunogenic cell death fails to elicit an immune response, immunogenic cell death specializes in antitumor immunity by modifying the surface composition of the cell and releasing soluble mediators, such as danger signals, to prompt elimination of the tumor cells. With advancement in understanding of immune cell types and pathways involved in the immune response, numerous preclinical studies have suggested that a combination of radiation and immunotherapy could lead to a propitious strategy against the challenges of cancer treatment. This paper examines the remedial adjustment of tumor immune responses and how it synchronizes efficiency and resilience to RT as well as its immunologic consequences.