Antitumor host immunity enhanced by near-infrared photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a novel antitumor therapy that selectively kills cancer cells by NIR light-triggered photochemical reaction of IRDye700DX within Ab-photoabsorber conjugates (APCs). NIR-PIT induces immunogenic cell death, causing immune cell migration between the tumor and tumor-draining lymph nodes, and expanding multiclonal tumor-infiltrating CD8⁺ T cells. Crucially, the cytotoxic effects of NIR-PIT are limited to cancer cells, sparing immune cells such as antigen-presenting cells and T cells, which are key players in boosting antitumor host immunity. By modifying the Ab used in APC synthesis, NIR-PIT can be repurposed to target and deplete noncancerous immunosuppressive cells including regulatory T cells, myeloid-derived suppressor cells, and cancer-associated fibroblasts in the tumor microenvironment. Immunosuppressive cell targeted NIR-PIT strongly potentiates antitumor host immunity, including the induction of abscopal effects and the development of immune memory. Furthermore, antitumor immune responses and therapeutic efficacy are synergistically enhanced when NIR-PIT is combined with other immune-activating treatments, such as interleukin-15 and immune checkpoint inhibitors. These new findings make NIR-PIT a valuable tool in the evolving landscape of cancer immunotherapy. This review explains the role of NIR-PIT in activating antitumor host immunity.