Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment  

作　　者：Yuting Zhang Guoqiang Liu Miaomiao Sun Xin Lu 

机构地区：[1]Department of Biological Sciences,Boler-Parseghian Center for Rare and Neglected Diseases,Harper Cancer Research Institute,University of Notre Dame,Notre Dame,IN 46556,USA [2]Integrated Biomedical Sciences Graduate Program,University of Notre Dame,Notre Dame,IN 46556,USA [3]Tumor Microenvironment and Metastasis Program,Indiana University Melvin and Bren Simon Cancer Center,Indianapolis,IN 46202,USA

出　　处：《Cancer Biology & Medicine》2020年第1期32-43,共12页癌症生物学与医学（英文版）

基　　金：partly supported by a graduate fellowship from China Scholarship Council(Grant No.201708340071);partly supported by a Career Catalyst Research Grant(Grant No.18548293)from the Susan G.Komen Foundation;a Cancer Research Grant from the Mary Kay Foundation;a Research Grant from the Elsa U.Pardee Foundation。

摘　　要：Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.

关 键 词：Tumor-associated neutrophil polymorphonuclear myeloid-derived suppressor cell IMMUNOSUPPRESSION cancer immunotherapy nanoparticle drug delivery 

分 类 号：R730.5[医药卫生—肿瘤]