Platinum-based chemotherapy in combination with PD-1/PD-L1 inhibitors: preclinical and clinical studies and mechanism of action
Yingyan Xue, Song Gao, Jingxin Gou, Tian Yin, Haibing He, Yanjiao Wang, Yu Zhang, Xing Tang, Rong Wu
Abstract
INTRODUCTION: Platinum chemotherapy is widely used in first-line treatment of patients with various cancers. PD-1/PD-L1 inhibitors have shown efficacy in several cancers, and the combination of platinum-based chemotherapy and PD-1/PD-L1 inhibitors has gradually become the focus of attention. Recently, the combination therapy has exhibited significant effects in preclinical models and clinical trials. AREAS COVERED: This review summarizes preclinical and clinical studies of the combination therapy in various cancers, and further explores mechanisms of the treatment. Furthermore, exploration of the mechanism demonstrates that the combination therapy plays a combination role in two ways. On the one hand, the positive effects of platinum-based chemotherapy on immunomodulation can be harnessed to increase the sensitivity of tumor cells to PD-1/PD-L1 inhibitors. On the other hand, platinum-based chemotherapy may upregulate PD-L1 expression in tumor tissue and exert a negative immunomodulatory effect, which can be counteracted by PD-1/PD-L1 inhibitors through their action pathway. What's more, different types of platinum-based chemotherapy exert different immunomodulation properties. EXPERT OPINION: This review describes a potential for the combination of PD-1/PD-L1 inhibitors and novel nanoparticles composed of platinum-loaded complex to yield positive effects in a wide range of doses, thus achieving higher therapeutic effects and lower side effects. ABBREVIATIONS: : half maximal inhibitory concentration; IFN: interferon; HLA: human leukocyte antigen; NK: natural killer cell; M6PR: mannose-6-phosphate receptor; GrzB: granzyme B; TNF: tumor necrosis factor.