Advancements in conventional cancer therapy combined with immunotherapy

Abstract Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells, reducing the overall tumor burden. Increasing evidence suggests that conventional therapies possess significant immunomodulatory properties in addition to their established direct tumoricidal effects. Emerging immunotherapies have revolutionized the clinical management of various cancer types. Conventional therapy and immunotherapy have demonstrated remarkable clinical efficacy, leading to numerous ongoing clinical investigations exploring their potential synergistic effects. However, trials investigating the combination of conventional therapy and immunotherapy have shown limited synergistic therapeutic efficacy. This unsatisfactory clinical outcome may be attributed to the suboptimal design of the combination approach and the inadequate understanding of the mechanisms and impacts of radiotherapy, chemotherapy, targeted therapy regimens (including dosing, timing, and administration route), and surgery on both cancer cells and the host immune system. Here, we comprehensively review preclinical and clinical investigations exploring the therapeutic effects and mechanisms of conventional therapy alone or in combination with immunotherapy. We proposed that optimizing the dosing, timing, and route of administration of conventional therapies can enhance the synergistic efficacy of combination therapies, thus offering significant clinical advantages.