IMPACT OF PROTON THERAPY ON TUMOR CELL IMMUNE RESPONSE

The immune response of tumor cells plays a key role in tumor radiation therapy. Boopathi et al. concluded that cancer cells killed by radiation therapy could trigger both innate and adaptive immune responses to help eliminate tumors. 77 Although proton therapy kills cells differently from photons and X‐rays, 55 , 56 the immune responses they induce may be similar at certain times. 78 Du et al. exposed the esophageal cancer cell line KYSE450 to X‐rays, protons, and carbon ion beams at a dose of 15 GyE/fraction. After 3 days of irradiation, they observed shared interferon and innate immune responses, including those related to interferon signaling and cytokine production regulation, which were dependent on the STING–STAT1 axis. 78 Furthermore, proton therapy failed to improve the clinical outcomes of NSCLC through radiation‐induced tumor immunity. 79 Nevertheless, it is unwise to conclude that proton therapy offers no benefits for immune response and tumor control, as previous studies were limited by their in vitro settings and small sample sizes. Proton therapy has a greater immunogenic effect than conventional photon therapy in olfactory neuroblastoma and NPC, which may enhance antitumor immune responses and the effectiveness of immunotherapeutic drugs. 80 In conclusion, rigorous in vivo and in vitro experiments should be conducted to clarify the effects of proton therapy on the immune responses of tumor cells.