摘要
Primary liver cancer,mainly hepatocellular carcinoma(HCC),is the sixth most diagnosed cancer and third leading cause of cancer-related death globally.Recently,immunotherapies such as immune checkpoint inhibitors(ICIs)have made great progress in the systemic treatment of HCC.However,anti-PD-1 therapy with pembrolizumab or nivolumab as a single agent did not meet their predefined end points of overall survival in the KEYNOTE-240 and Check Mate 459 trials.It is urgent to understand the immunological rationale and explore novel ways to improve the efflcacy of immunotherapy.The combination of ICIs with other therapies,such as tyrosine kinase inhibitors(TKIs),monoclonal antibodies,or local therapy,has been demonstrated to improve overall response rate and survival.In addition,modulating tumor microenvironment is a potential way to overcome the primary and secondary resistance to immunotherapies.In this review,we summarized the latest findings in the immune microenvironment,the mechanisms of their synergistic effects when combined with anti-VEGF agents or TKIs,as well as other kinds of immune treatment.
基金
supported by grants from the National Natural Science Foundation of China(81902390)
the Major Program of National Natural Science Foundation of China(91959203)
the Key Program of the National Natural Science Foundation of China(81930074)。
