Targeted Nanophotoimmunotherapy Potentiates Cancer Treatment by Enhancing Tumor Immunogenicity and Improving the Immunosuppressive Tumor Microenvironment

Cancer immunotherapy, such as immune checkpoint blockade, chimeric antigen receptor, and cytokine therapy, has emerged as a robust therapeutic strategy activating the host immune system to inhibit primary and metastatic lesions. However, low tumor immunogenicity (LTI) and immunosuppressive tumor microenvironment (ITM) severely compromise the killing effect of immune cells on tumor cells, which fail to evoke a strong and effective immune response. As an exogenous stimulation therapy, phototherapy can induce immunogenic cell death (ICD), enhancing the therapeutic effect of tumor immunotherapy. However, the lack of tumor targeting and the occurrence of immune escape significantly reduce its efficacy in vivo, thus limiting its clinical application. Nanophotoimmunotherapy (nano-PIT) is a precision-targeted tumor treatment that co-loaded phototherapeutic agents and various immunotherapeutic agents by specifically targeted nanoparticles (NPs) to improve the effectiveness of phototherapy, reduce its phototoxicity, enhance tumor immunogenicity, and reverse the ITM. This review will focus on the theme of nano-PIT, introduce the current research status of nano-PIT on converting cold tumors to hot tumors to improve immune efficacy according to the classification of immunotherapy targets, and discuss the challenges, opportunities, and prospects.

Automated summary

Cancer immunotherapy is an effective treatment strategy, but low tumor immunogenicity and immunosuppressive tumor microenvironment compromise its effectiveness. Phototherapy can enhance the therapeutic effect of tumor immunotherapy, but its efficacy is limited in vivo. Nanophotoimmunotherapy combines phototherapy and immunotherapy using targeted nanoparticles to improve the efficacy of phototherapy, reduce its toxicity, enhance tumor immunogenicity, and reverse the tumor microenvironment. This review focuses on the current research status, challenges, opportunities, and prospects of nano-PIT in converting cold tumors to hot tumors to improve immune efficacy.