肿瘤化学免疫治疗是免疫疗法与化学疗法相结合通过协同作用治疗肿瘤的一种新方法。以铂类药物为代表的金属药物是一类重要的化学抗肿瘤药物，其作用机理是与肿瘤细胞DNA形成交联物并阻止其复制；但是，这类药物存在严重的毒性和耐药性问题。近年来发现有些金属配合物在产生细胞毒性的同时，也通过多种机制参与机体的免疫调节过程，其中以诱导免疫原性细胞死亡（ICD）最为常见。本文简要介绍了肿瘤化学免疫治疗的基本概念以及与免疫抑制有关的肿瘤微环境，概述了金属配合物的免疫活性和调节免疫过程的基本原理，并以铂类药物为例总结了金属配合物调节免疫过程的可能途径，最后列举了若干具有ICD诱导潜力和其他免疫调节功能的非铂类金属配合物，指出了目前化学免疫治疗存在的问题和未来的应用潜力。化学治疗与免疫治疗结合既可以利用机体免疫系统增强金属配合物的抗肿瘤效果，又可以减少药物剂量，降低毒副作用，是设计金属抗肿瘤药物的新方向之一。
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
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