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Therapeutic modulation of the CD47-SIRpαaxis in the pediatric tumor microenvironment:working up an appetite

Cancer Drug Resistance 2020年第3期3卷 550-562页

作者： Ajay Gupta Cenny Taslim Brian p.Tullius timothy p.cripe Division of Hematology OncologyBlood and Marrow TransplantNationwide Children’s HospitalColumbusOH 43205USA. Center for Childhood Cancer and Blood Diseases Nationwide Children’s HospitalColumbusOH 43205USA.

Evasion of immune surveillance is one of the hallmarks of *** the adaptive immune system has been targeted via checkpoint inhibition,many patients do not sustain durable remissions due to the heterogeneity of the tumor microenvironment,so additional strategies are *** innate immune system has its own set of checkpoints,and tumors have co-opted this system by expressing surface receptors that inhibit *** of these receptors,CD47,also known as the“don’t eat me”signal,has been found to be overexpressed by most cancer histologies and has been successfully targeted by antibodies blocking the receptor or its ligand,signal regulatory proteinα(SIRpα).By enabling phagocytosis via antigen-presenting cells,interruption of CD47-SIRpαbinding leads to earlier downstream activation of the adaptive immune *** and ongoing clinical trials are demonstrating the safety and efficacy of CD47 blockade in combination with monoclonal antibodies,chemotherapy,or checkpoint inhibitors for adult cancer *** aim of this review is to highlight the current literature and research on CD47,provide an impetus for investigation of its blockade in pediatric cancer histologies,and provide a rationale for new combination therapies in these patients.

关键词： CD47 SIRpα immunotherapy tumor microenvironment pediatric cancer innate immune system checkpoint inhibitor phagocytosis

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