Crosstalk between the B7/CD28 and EGFR pathways:Mechanisms and therapeutic opportunities  

作　　者：Xiaoxin Ren Yixian Li Christopher Nishimura Xingxing Zang 

机构地区：[1]Department of Microbiology and Immunology,Albert Einstein College of Medicine,New York,NY 10461,USA [2]Division of Pediatric Hematology/Oncology/Transplant and Cellular Therapy,Children's Hospital at Montefiore,Bronx,NY 10467,USA [3]Department of Medicine,Albert Einstein College of Medicine,New York,NY 10461,USA [4]Department of Urology,Albert Einstein College of Medicine,New York,NY 10461,USA

出　　处：《Genes & Diseases》2022年第5期1181-1193,共13页基因与疾病（英文）

基　　金：supported by NIH R01CA175495 and R01DK100525,Department of Defense BC190403,Irma T.Hirschl/Monique Weill-Caulier Trust,and Cancer Research Institute.

摘　　要：Somatic activating mutations in the epidermal growth factor receptor(EGFR)are one of the most common oncogenic drivers in cancers such as non-small-cell lung cancer(NSCLC),metastatic colorectal cancer,glioblastoma,head and neck cancer,pancreatic cancer,and breast cancer.Molecular-targeted agents against EGFR signaling pathways have shown robust clinical efficacy,but patients inevitably experience acquired resistance.Although immune checkpoint inhibitors(ICIs)targeting PD-1/PD-L1 have exhibited durable anti-tumor responses in a subset of patients across multiple cancer types,their efficacy is limited in cancers harboring activating gene alterations of EGFR.Increasing studies have demonstrated that upregulation of new B7/CD28 family members such as B7-H3,B7x and HHLA2,is associated with EGFR signaling and may contribute to resistance to EGFR-targeted therapies by creating an immunosuppressive tumor microenvironment(TME).In this review,we discuss the regulatory effect of EGFR signaling on the PD-1/PD-L1 pathway and new B7/CD28 family member pathways.Understanding these interactions may inform combination therapeutic strategies and potentially overcome the current challenge of resistance to EGFR-targeted therapies.We also summarize clinical data of anti-PD-1/PD-L1 therapies in EGFR-mutated cancers,as well as ongoing clinical trials of combination of EGFR-targeted therapies and anti-PD-1/PD-L1 immunotherapies.

关 键 词：Combination therapies EGFR Immune checkpoint blockade New B7/CD28 members PD-1/PD-L1 pathway 

分 类 号：R730.51[医药卫生—肿瘤]