Photoimmunotherapy for cancer treatment based on organic small molecules: Recent strategies and future directions

Photodynamic therapy (PDT) is considered as a promising anticancer approach, owning to its high efficiency and spatiotemporal selectivity. Ample evidence indicated that PDT can trigger immunogenic cell death by releasing antigens that activate immune cells to promote anti-tumor immunity. Nevertheless, the inherent nature of tumors and their complex heterogeneity often limits the efficiency of PDT, which can be overcome with a novel strategy of photo-immunotherapy (PIT) strategy. By exploring the principles of PDT induction and ICD enhancement, combined with other therapies such as chemotherapy or immune checkpoint blockade, the tailored solutions can be designed to address specific challenges of drug resistance, hypoxic conditions, and tumor immunosuppressive microenvironments (TIMEs), which enables targeted enhancement of systemic immunity to address most distant and recurrent cancers. The present article summarizes the specific strategies of PIT and discusses recent existing limitations. More importantly, we anticipate that the perspectives presented herein will help address the clinical translation challenges associated with PIT.