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Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Photoactivated Ruthenium-Platinum Complex Enhances Immune Checkpoint Blockade Therapy by Upregulating MHC-I

Liu-Yi Liu^1,2, Jiazheng Li¹, Peng Sun²

¹State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Journal of Medicinal Chemistry

|February 17, 2026

Summary

A novel ruthenium-platinum complex enhances cancer immunotherapy by upregulating MHC-I and inducing immunogenic cell death. This metal-based photodynamic therapy overcomes tumor immune evasion and synergizes with checkpoint inhibitors for improved antitumor responses.

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Area of Science:

Biomedical Engineering
Cancer Research
Immunology

Background:

Cancer immunotherapy faces challenges due to tumor immune evasion, often caused by Major Histocompatibility Complex class I (MHC-I) downregulation.
Developing strategies to overcome immune evasion is crucial for enhancing the efficacy of cancer treatments.

Purpose of the Study:

To design and evaluate a novel trinuclear ruthenium-platinum complex (TriRuPt) as a photosensitizer for photodynamic therapy (PDT).
To investigate TriRuPt's ability to overcome tumor immune evasion and enhance antitumor immunity.

Main Methods:

Rational design of a trinuclear ruthenium-platinum complex (TriRuPt).
Utilizing TriRuPt as a photosensitizer in photodynamic therapy (PDT) to generate reactive oxygen species.
Assessing MHC-I upregulation and induction of immunogenic cell death (ICD).
Evaluating the synergistic effects of TriRuPt-PDT with immune checkpoint inhibitors in vivo.

Main Results:

TriRuPt demonstrated light-induced nuclear translocation and metal-enhanced photooxidation.
TriRuPt-mediated PDT induced MHC-I upregulation and immunogenic cell death (ICD).
Combined TriRuPt-PDT and immune checkpoint inhibitors significantly suppressed tumor growth, reprogrammed the tumor microenvironment, and enhanced adaptive immune responses.

Conclusions:

TriRuPt represents a promising metal-based dual immunomodulatory strategy to potentiate immune checkpoint blockade therapy.
This approach effectively overcomes tumor immune evasion and resistance in cancer immunotherapy.
Transition metal complexes possess underexplored immunoregulatory properties with significant therapeutic potential.