Clinical application of high-LET radiotherapy combined with immunotherapy in malignant tumors

The superior physical and biological properties of high linear energy transfer (LET), as opposed to traditional low-LET rays, underscore the advantage of proton therapy (PRT) and carbon ion radiotherapy (CIRT) are better than traditional photon radiotherapy (XRT). With the advancements in science, an increasing number of hospitals have introduced new technologies. However, radiotherapy is primarily used for local treatment, which means that if the tumor has metastasized to distant sites, it is often necessary to combine it with systemic therapies such as immunotherapy. In recent years, the combination of high-LET radiotherapy and immunotherapy has emerged as a promising treatment option in oncology and many studies have confirmed its efficacy for both local and distant metastases. In this review, we summarize the effects of PRT and CIRT on the immune system in detail, followed by an introduction to preclinical and clinical studies of PRT and CIRT in combination with immune checkpoint inhibitor (ICIs) therapy. We also briefly introduce some preclinical studies on CIRT in combination with dendritic cells (DCs) and Treg inhibitor therapies.