Tumor chemoimmunotherapy is a new method for the treatment of tumors through the combination of immunotherapy and chemotherapy taking advantage of synergistic effect. Metal drugs, represented by platinum agents, are important chemotherapeutic antitumor drugs with cross-linking DNA and preventing DNA replication as the mechanism of action. Nevertheless, these drugs have severe general toxicity and drug resistance. In recent years it was found that in addition to producing cytotoxicity, some metal complexes are involved in the immunomodulation by various mechanisms, including the most common induction of immunogenic cell death (ICD). This review introduces the basic concepts of tumor chemoimmunotherapy and the tumor microenvironment related to immunosuppression, outlines the immune activities and basic principles for immunomodulation of metal complexes like those of platinum. Finally, some non-platinum metal complexes with ICD-inducing potentials and other immunomodulating functions are described, and the existing problems and application potential of chemoimmunotherapy in the future are indicated. The combination of chemotherapy and immunotherapy not only makes use of the human immune system to enhance the antitumor effect of metal complexes, but also reduces the dose and toxic side effects of drugs, and therefore is one of the new directions for the design of metal-based antitumor drugs.
Contents
1 Introduction
1.1 Tumor immunotherapy and chemotherapy
1.2 Immunosuppressive tumor microenvironment
2 Metal complexes and chemoimmunotherapy
2.1 Immunocompetence of metal complexes
2.2 Immunomodulation effect of metal complexes
2.3 Immunogenic cell death
3 Chemoimmunotherapeutic effect of platinum-based drugs
3.1 Potential pathways for platinum-based drugs participating in immunomodulation
3.2 Platinum complexes with ICD-inducing effect
3.3 Chemoimmunotherapeutic platinum complexes
3.4 Combination of platinum-based drugs with other drugs for chemoimmunotherapy
4 Immunostimulation potential of non-platinum complexes
5 Conclusion and outlook