Combined carbon ion radiotherapy and immunotherapy: leveraging the immunological advantages of carbon ion

Immunotherapy represents a systemic approach to cancer treatment; however, its effectiveness can be limited by intrinsic tumor resistance or immunosuppressive mechanisms within the tumor microenvironment. In contrast, carbon ion radiotherapy (CIRT) demonstrates considerable immunomodulatory potential owing to its distinct biological properties. The exposure of tumor-associated antigens, increased immune cell infiltration and activity, and modifications in the immune microenvironment after CIRT provide a mechanistic rationale for combining CIRT with immunotherapy. Furthermore, strategies aimed at converting the tumor microenvironment from immunosuppressive to immunostimulatory, or those targeting immune checkpoints, are currently under active exploration. This review summarizes the latest advances in combining heavy ion radiotherapy with immunotherapy, encompassing both preclinical and clinical studies. Based on the immunological advantages of CIRT, it provides a comprehensive summary and in-depth exploration of the potential of this combined treatment modality for future clinical applications, along with a theoretical foundation to support it.