Improving antitumor immunity using antiangiogenic agents:Mechanistic insights,current progress,and clinical challenges  

作　　者：Shu-Jin Li Jia-Xian Chen Zhi-Jun Sun 

机构地区：[1]The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine,Ministry of Education,School and Hospital of Stomatology,Wuhan University,Wuhan,Hubei 430079,P.R.China [2]Department of Oral Maxillofacial-Head Neck Oncology,School and Hospital of Stomatology,Wuhan University,Wuhan,Hubei 430079,P.R.China

出　　处：《Cancer Communications》2021年第9期830-850,共21页癌症通讯（英文）

基　　金：National Key Research and Development Program,Grant/Award Number:2017YFSF090107;National Natural Science Foundation of China,Grant/Award Numbers:82072996,81874131;Hubei Province Natural Science Funds for Distinguished Young Scholar,Grant/Award Number:2017CFA062;Innovative research team of high-level local universities in Shanghai,Grant/Award Number:ZLCX20180500。

摘　　要：Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy can ultimately relapse and progress.Thus,some studies have investigated combining immunotherapy with other therapies to overcome resistance to monotherapy.Recently,multiple preclinical and clinical studies have shown that tumor vasculature is a determinant of whether immunotherapy will elicit an antitumor response;thus,vascular targeting may be a promising strategy to improve cancer immunotherapy outcomes.A successful antitumor immune response requires an intact“Cancer-Immunity Cycle,”including T cell priming and activation,immune cell recruitment,and recognition and killing of cancer cells.Angiogenic inducers,especially vascular endothelial growth factor(VEGF),can interfere with activation,infiltration,and function of T cells,thus breaking the“Cancer-Immunity Cycle.”Together with immunostimulation-regulated tumor vessel remodeling,VEGF-mediated immunosuppression provides a solid therapeutic rationale for combining immunotherapy with antiangiogenic agents to treat solid tumors.Following the successes of recent landmark phase III clinical trials,therapies combining immune checkpoint inhibitors(ICIs)with antiangiogenic agents have become first-line treatments for multiple solid tumors,whereas the efficacy of such combinations in other solid tumors remains to be validated in ongoing studies.In this review,we discussed synergies between antiangiogenic agents and cancer immunotherapy based on results from preclinical and translational studies.Then,we discussed recent progress in randomized clinical trials.ICI-containing combinations were the focus of this review because of their recent successes,but combinations containing other immunotherapies were also discussed.Finally,we attempted to define critical challenges in combining ICIs with antiangiogenic agents to promote coordination and stimulate

关 键 词：ANTIANGIOGENESIS BEVACIZUMAB cancer combination therapy immune-checkpoint inhibitor IMMUNOTHERAPY vascular endothelial growth factor 

分 类 号：R73[医药卫生—肿瘤]