Photoimmunotherapy for cancer treatment based on organic small molecules: Recent strategies and future directions
Deming Zhao, Xin Wen, Jiani Wu, Feihong Chen
Abstract
• The revelation that photodynamic therapy may induce immunogenic cell death, consequently triggering abscopal effect akin to radiotherapy, has emerged. • Structural optimization of the photosensitizer not only increases reactive oxygen species production but also enhances organelle targeting and intracellular metabolic capacity, resulting in a more efficient induction of immunogenic cell death. • The introduction of additional components, such as immune checkpoint inhibitors, delivered concurrently, allows for the formulation of personalized strategies tailored to specific scenarios. • The integration of multiple components introduces challenges, including potential conflicts in therapeutic effects, issues of toxicity and metabolism, and the crucial need for carefully selecting in vivo models to assess photoimmunotherapy. Addressing these challenges is imperative for the swift clinical translation of this promising approach. 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.