性别对新型透明细胞肾细胞癌小鼠模型免疫监视和转移趋向性的影响.pdf

1、Influence of sex on immunosurveillance and metastatic tropism in novel mouse models of clear cell renal cell carcinomaDoris Zheng1,2,Hui Jiang1,2,Nicole Rittenhouse1,2,Amrita Nargund Mangalvedhekar1,2,Zizhuo Yang1,2,5,Liangliang Ji4,David B.Solit1,3,Lynda Vuong1,2 A.Ari Hakimi1,21Human Oncology and

2、Pathogenesis Program,Memorial Sloan-Kettering Cancer Center,NY,NY,2Department of Surgery/Urology Service,MSKCC,NY,NY,3Department of Medicine,MSKCC,NY,NY,4 Immunology Program,Sloan Kettering Institute,NY,NY 5Department of Urology,QiluHospital,Cheeloo College of Medicine,Shandong University,Shandong,C

3、hinaSex dimorphism exists in RCCRCC occurs in males at twice the rate.Haupt et al Nat.Reviews Cancer 2021The mortality rate is more than twice as high.SLIDE DIMENSIONS SHOULD FOLLOW 16:9 RATIOMany reasons for sex bias have been exploredEscape from X-Inactivation Tumor Suppressor(EXITS)genesLoss of Y

4、-ChromosomeSmokingAndrogensCD8+T-cell ExhaustionEnhanced immunityWhat role does the immune system play in gender disparity?Sex dimorphism can be seen in Vhl-/-p53-/-Rb1-/-ccRCC GEMM model 0200400600020406080100Days after Tamoxifen%without tumorkVpR GEMMMaleFemale0.0001P=Harlander et al.Nature Medici

5、ne 2017Lynda VuongNovel RCC models recapitulate human diseaseVhl-/-p53-/-Rb1-/-Myc-overexpressionLVRCC67(ICB-Resistant):01020304002004006008001000DaysTumor Vol(mm3)aPD-1Control-20-100102050010001500DayVolume(mm3)IgGCTLA-4PD-1+CTLA-4*-20-100102050010001500DayVolume(mm3)IgGCTLA-4PD-1+CTLA-4*VhlmutBap1

6、-/-Cdkn2a/2b-/-HJRCC68N(ICB-Responsive):Rappold&Vuong eat al.Cancer Discovery 2022Hui Jiang et al.UnpublishedSex bias in orthotopic primary tumors is dependent on the immune systemMF010002000300040005000NSGTumor Weight(mg)0.2857MF0100020003000WTTumor Weight(mg)0.1143MF0200400600NSGTumor Weight(mg)MF