Radiation therapy in the era of precision medicine: a narrative review

Radiotherapy (RT) not only induces lethal DNA damage in tumor cells but also modulates the tumor immune microenvironment (TIME). It enhances the release of pro-inflammatory mediators and promotes infiltration of cytotoxic immune cells. However, RT can also lead to the accumulation of immunosuppressive cells, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs), which may contribute to an immunosuppressive milieu. In this review, we aim to delineate the principal issues pertaining to the immunoregulatory effects of RT.

A PubMed search was conducted for articles from the past decade using the terms: (radiation therapy or conformal radiotherapy) AND (immunogenic cell death, cyclic GMP-AMP synthase, tumor immune microenvironment, anoxia, immune checkpoint inhibition, or low-dose radiotherapy).

This review provides a comprehensive analysis of the immunostimulatory effects of RT, emphasizing its ability to induce immunogenic cell death (ICD), activate the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, and modulate immune cell populations within the tumor microenvironment (TME). It also explores how different radiation doses, fractionation schemes, and planning parameters influence these biological effects. Importantly, conformal RT remains integral to cancer treatment by enabling the delivery of higher radiation doses precisely to tumors while sparing surrounding healthy tissues.

RT exerts anti-tumor effects by triggering ICD, activating the cGAS/STING signaling pathway, and reshaping the TIME. These effects vary depending on radiation dose and fractionation. Conformal RT optimizes therapeutic outcomes by targeting tumors with high precision, minimizing toxicity to normal tissues.