肿瘤逃逸机制.docx

肿瘤免疫逃逸机制与免疫 生4^^ 生4^^打对乘 华中科技大学同济医学院教研组 ■ 一肿瘤相关的抑制分子 ■抑制性细胞因子； IL-10, TGF-b,... ■抑制性膜分子； B7-H1, B7-H4, HLA-G,... ■其他小分子抑制物 No 寸 二肿瘤相关的抑制细胞 ■ CD4+CD25+ Foxp3 + Treg; ■髓性来源的抑制细胞(myeloid-derived suppressor cell, MDSC); ■肿瘤相关的巨噬细胞(tumor-associated macrophage, TAM); Monocytes GM-CSF ■ LPS/ IFNV Bacterial products gjgfjgj M-CSF IL-4 IL-13 IL-10 Corticosteroids PGE VitD3 IL-1 TNF IL-12 CXCL-9 CXCL-10 CXCL-11 RNI ROI Classical M1 Macrophages Alternative M2 Macrophages IL-1 ra decoy IL-1RII tL-10 CCL17 CCL18 CCL22 Polyamine Scavenger R Mannose R Tumor Suppression Immunostimulation Tumor Promotion Immunosuppression Defence Against Bacteria Inflammatory Cytokine Production Tissue Repair and Angiogenesis Scavenging TissueMacrophages CCL1CD86, MHCII CCL1 CD86, MHCII IL-1, IL-6, IL-10,TNF-a IL-10, TGF? TLR1,TLR8, CD163,CCR2 Polyamine IL-10, TGFp,IL-1ra CCL17,CCL22,CCL24 SR, MR, CD163, Decoy IL-1RII, MHCII Molecular pathways of macrophage polarization and their role in tumor progression  TAMs originate from blood monocytes recruited at the tumor site by molecules produced by neoplastic and by stromal cells Metastasis MMP2. MMP9,EGF. Wnr 5aCSF-1. Sema4DIL-1(3. Cathepsin B TGF-B.VEGF MMonocyte RecrultmftntCSF.IL-10,Differentiation and M2- PolarisationVEGF M Monocyte Recrultmftnt CSF. IL-10, Differentiation and M2- Polarisation VEGF MMPs.CSF-1 AngiogenesisTumorPromotionCXCL 8. CXCL-12 Angiogenesis TumorPromotion VEGR IL-10. MMPs .TGF?B. M-CSF, ECM Proteins MonocyteBlood VesselTumor CellM2 MacrophageArginase 1.CCL17.CCL22. CCL18. IL-10Down Regulation of Adaptive Immunity Monocyte Blood Vessel Tumor Cell M2 Macrophage Arginase 1.CCL17. CCL22. CCL18. IL-10 Down Regulation of Adaptive Immunity 寸三抑制抗肿瘤效应细胞 ■ 抑制NK细胞杀伤活性； 肿瘤细胞上表达KAR配体MICA/MICB下降; 2肿瘤灶局部MMP可将MICA、MICB降解为可溶分子，封闭NKG2D (KAR) 3肿瘤微环境中IL-10、TGF-b可抑制NK细胞杀伤活性： . 抑制T细胞激活和功能； 1 .肿瘤细胞表面共刺激分子(B7-l,B7-2)、MHCII分子和Fas等表达下降: 肿瘤细胞分泌IL-10、TGF-b抑制性细胞因子； 肿瘤灶局部侵润Treg、MDSC、iDC等具有负性调节作用的细胞； 肿瘤细胞合成与分泌多种具有负性调节作用的活性分子，如NO、ID。等 四肿瘤细胞直接逃逸免疫监