Combined treatment of small cell lung cancer using radiotherapy and immunotherapy: Challenges and updates

Currently, chemotherapy remains the standard first- and second-line treatment for small cell lung cancer (SCLC). Research concerning immunotherapy has brought about a remarkable development in the treatment pattern of SCLC. Atirizumab, duvalizumab, atezolizumab, and serplulimab can significantly improve the clinical outcomes of SCLC. Given the rapidly evolving concept that combining immunotherapy with radiotherapy can increase therapeutic effectiveness, clinicians are devoted to further improving local tumor control by integrating immunotherapy with radiotherapy. This paper reviews the research progress in this field to date and explores ways to further enhance the efficacy of this combination therapy. We first discussed that immunotherapy combined with radiotherapy can improve the abscopal effect, progression-free survival, and overall survival rates of SCLC patients. Then, the biomarkers related to the radiation immune microenvironment, such as programmed death ligand-1 (PD-L1), tumor mutational burden (TMB), and the immune function of patients were discussed. Next, we explored the occurrence and underlying mechanisms of immune resistance during radiotherapy implementation. Finally, we clarified that the emerging trend of low-dose radiotherapy help overcome the inhibitory signals that limit T-cell infiltration in the tumor matrix. In summary, considering the rapid development of this field, these combined therapy strategies may have unlimited potential to further improve the efficacy of radiotherapy combined with immunotherapy for patients.