Host Immunity Following Near-Infrared Photoimmunotherapy Is Enhanced with PD-1 Checkpoint Blockade to Eradicate...

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Near-infrared photoimmunotherapy (NIR-PIT) induces immunogenic cell death but often fails to generate durable antitumor responses.
• Adaptive immune resistance is a potential barrier to sustained efficacy after NIR-PIT treatment.

Purpose of the Study:

• To investigate the combination of NIR-PIT targeting CD44 with PD-1 blockade in syngeneic tumor models.
• To determine if this combination can overcome adaptive immune resistance and induce durable antitumor immunity.

Main Methods:

• Utilized multiple syngeneic tumor models in mice.
• Administered NIR-PIT targeting CD44 alone or in combination with PD-1 blockade.
• Assessed tumor growth, immune cell infiltration (dendritic cells), and tumor antigen-specific T-cell responses (preexisting and de novo).

Main Results:

• NIR-PIT monotherapy halted tumor growth and induced de novo T-cell responses in two of three models.
• Combination therapy reversed adaptive immune resistance, enhancing both preexisting and de novo T-cell responses.
• Complete rejection of MC38 tumors and systemic antitumor immunity, including immune memory, were observed with combination treatment.

Conclusions:

• Combining NIR-PIT with PD-1 blockade effectively reverses adaptive immune resistance.
• This strategy induces robust innate and adaptive immunity, leading to significant tumor growth control and rejection.
• Tumor antigenicity is a key factor influencing response to combination therapy, with antigenic models showing higher efficacy.