Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy

T regulatory cells, or T_regs for short, are immunosuppressive cells that not only suppress excess inflammation but also interfere with anticancer immunity. Sato et al. developed a way to selectively deplete T_regs in tumors to promote antitumor effects while minimizing the risk of autoimmunity. To achieve this goal, the authors used a method termed near-infrared photoimmunotherapy, where part of an antibody that recognizes T_regs is fused to a light-sensitive dye, and shining near-infrared light on the tumor activates the antibody and triggers killing of the T_regs. Mice subjected to this treatment not only killed the targeted tumor but also could even destroy untreated tumors of the same type located in other parts of the body, suggesting the potential for treatment of metastatic disease.

Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting antitumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4⁺CD25⁺Foxp3⁺ regulatory T cells (T_regs) are well-known immunosuppressor cells that play a key role in tumor immunoevasion and have been the target of systemic immunotherapies. We used CD25-targeted near-infrared photoimmunotherapy (NIR-PIT) to selectively deplete T_regs, thus activating CD8 T and natural killer cells and restoring local antitumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of T_regs, thereby providing an alternative approach to cancer immunotherapy.