Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity 英文参考文献.docVIP

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Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity 英文参考文献.doc

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Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity 英文参考文献

AntitumorEffectofMalariaParasiteInfectioninaMurine LewisLungCancerModelthroughInductionofInnate andAdaptiveImmunity LiliChen1,3,ZhengxiangHe1,3,LiQin1,3,QinyanLi1,3,XibaoShi1,SitingZhao1,LingChen1 ,Nanshan Zhong2*,XiaopingChen1,3* 1Center for Infection and Immunity, State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China, 2StateKey Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, FirstAffiliatedHospital,GuangzhouMedical University, Guangzhou,China,3CAS-FSBiotechandPharmaceuticalCenter,ChineseAcademyofSciences,Foshan,China Abstract Background: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatmentisavailable.Developingnewtherapeuticstrategiesforlungcancerisurgentlyneeded.Malariahasbeenreported tostimulatehostimmuneresponses,whicharebelievedtobeefficaciousforcombatingsomeclinicalcancers.Thisstudyis aimedtoprovideevidencethatmalariaparasiteinfectionistherapeuticforlungcancer. Methodology/Principal Findings: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infectedwithmalariarevealedthatangiogenesiswasinhibited,whichcorrelatedwithincreasedterminaldeoxynucleotidyl transferase-mediated(TUNEL)staininganddecreasedKi-67expressionintumors.Throughnaturalkiller(NK)cellcytotoxicity activity,cytokineassays,enzyme-linkedimmunospotassay,lymphocyteproliferation,andflowcytometry,wedemonstrated thatmalariainfectionprovidedanti-tumoreffectsbyinducingbothapotentanti-tumorinnateimmuneresponse,including thesecretionofIFN-candTNF-a andtheactivation ofNKcells aswellasadaptive anti-tumor immunitywithincreasing tumor-specific T-cell proliferation and cytolytic activity