Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer

Immune checkpoint blockade (ICB) therapy has evolved as a revolutionized therapeutic modality to eradicate tumor cells by releasing the brake of the antitumor immune response. However, only a subset of patients could benefit from ICB treatment currently. Phototherapy usually includes photothermal therapy (PTT) and photodynamic therapy (PDT). PTT exerts a local therapeutic effect by using photothermal agents to generate heat upon laser irradiation. PDT utilizes irradiated photosensitizers with a laser to produce reactive oxygen species to kill the target cells. Both PTT and PDT can induce immunogenic cell death in tumors to activate antigen-presenting cells and promote T cell infiltration. Therefore, combining ICB treatment with PTT/PDT can enhance the antitumor immune response and prevent tumor metastases and recurrence. In this review, we summarized the mechanism of phototherapy in cancer immunotherapy and discussed the recent advances in the development of phototherapy combined with ICB therapy to treat malignant tumors. Moreover, we also outlined the significant progress of phototherapy combined with targeted therapy or chemotherapy to improve ICB in preclinical and clinical studies. Finally, we analyzed the current challenges of this novel combination treatment regimen. We believe that the next-generation technology breakthrough in cancer treatment may come from this combinational win-win strategy of photoimmunotherapy.