Cancer Immunity and Radiotherapy

Cancer immunotherapy has revolutionized the treatment of many cancers, yet it often yields limited and transient responses as a standalone approach. This has prompted interest in combining immunotherapy with other treatments to enhance efficacy. Radiotherapy, a standard oncological treatment responsible for around 40% of cancer cures, has emerged as a promising complement to immunotherapy. Radiotherapy induces immunogenic cell death through DNA damage, which stimulates immune responses. This process activates inflammatory cytokine signaling and promotes the release of damage-associated molecular patterns (DAMPs), leading to enhanced antigen presentation and activation of cytotoxic T cells. However, radiotherapy also produces reactive oxygen species (ROS), TGFβ, CXCL12, and other factors that activate T-reg cells, myeloid-derived suppressor cells, and cancer-associated fibroblasts, leading to immunosuppressive effects. Understanding the immune effects of radiotherapy and developing innovative strategies that leverage the strengths of both radiotherapy and immunotherapy could help address their respective limitations. Such advancements have the potential to significantly improve therapeutic outcomes for cancer patients.

- Mechanistic insights into the immune effects of radiotherapy: studies elucidating the molecular mechanisms, genes, and pathways that mediate the beneficial or detrimental immune effects.
- Novel anti-tumor combination therapies and their mechanisms: Contributions highlighting the potential synergies between radiotherapy and modern immunotherapies, such as immune checkpoint inhibitors, personalized tumor vaccines, immune cell engagers, and adoptive cell transfer therapy.
- Advances in radiotherapy regimens that amplify the immune response: Research exploring optimal irradiation doses, timings, and intervals to sustain and enhance the anti-tumor immune response.
- Innovations in radiation-based therapeutics: Developments in radiation-based therapeutic platforms, including irradiated engineered nanoparticles, tumor cells, tumor cell-derived microparticles, and extracellular vesicles that catalyze anti-tumor immunotherapy.
- Biomarkers of radiation-induced immunity: Novel biomarkers that identify patients who benefit from radiotherapy-immunotherapy combinations and guide their delivery.
- Radiotherapy-induced immune effects and toxicity: Investigation into radiotherapy-induced normal tissue toxicity and the potential immune crosstalk.