中国人民解放军陆军军医大学（第三军医大学）：《生物技术制药》课程教学资源（PPT课件）08 专题研讨汇报课（胃癌免疫治疗的研究策略）

《生粉莪制药》 专题研 庄园 副研究员 国家免疫生物制品工程技术研究中心 暨全军免疫生物制品重点实验室

庄 园 副研究员 国家免疫生物制品工程技术研究中心 暨全军免疫生物制品重点实验室 专题研讨课 《生物技术制药》

一题 研讨主题 “胃漓兔蜜治疗的研究略” vAccine fluzone

微生物与生化药学教研室 研讨主题 “胃癌免疫治疗的研究策略

Introduction of concept Cancer Immunoediting”(难点) Immunotherapy in gastric cancer (重点) Immunity cancer-editing Clinic to basic(启示)

•Introduction of concept “Cancer Immunoediting” (难点) •Immunotherapy in gastric cancer (重点) • “Immunity cancer-editing” Clinic to basic (启示)

Introduction ● Immunity- nature??? o Recognization----self or nonself immunogenicity(免疫原性) o Balance immune tolerance immunoreactivity(免疫反应性)orRE5 Iune response Cancer Immunoediting???

Introduction • Immunity----nature ??? • Recognization----self or nonself • Balance------immune tolerance or immune response “Cancer Immunoediting???” immunogenicity (免疫原性) immunoreactivity (免疫反应性)

Three Ways for Self Antigens to Become Tumor Antigens MHC Peptides C molecules Mutant Normal protein Modified proteins Overexpressed protein rotein umor ce Tumor cell Tumor cell 质变 量变 伪装 Mutation Overexpression Post-Translational Modification 2 Self Nonself

Three Ways for Self Antigens to Become Tumor Antigens Self Nonself 质变 量变 伪装

immunodeficient mice免疫缺陷小鼠 Carcinogen 致癌剂 200 days 100 mice Immunocompetent Carcinogen E53E 40 致癌剂 200 days 820 160 Time after carcinogen treatment (days) mmunocompetent mice免疫正常小鼠 The immune status of mice is a critical determinant of their susceptibility to tumors induced by chemical carcinogen 免疫状态影响成瘤

The immune status of mice is a critical determinant of their susceptibility to tumors induced by chemical carcinogen 免疫状态影响成瘤 Immunodeficient mice 免疫缺陷小鼠 Immunocompetent mice 免疫正常小鼠 Carcinogen 致癌剂 200 days Carcinogen 致癌剂 200 days

Primary tumor Tumor Inject into Monitor Growth growing In cell line naive Wt tumor profile recipients growth Edited progressor Immunocompetent Day 30 Mouse免疫正常小鼠 Immunocompetent Mouse免疫正常小鼠 多 Unedited progressor 0 Day 30 Immunodeficient Unedited Mouse免疫缺陷小鼠 regressor 0 Day 3 Tumors in immunocompetent mice are qualitatively different from tumors in immunodeficient mice 不同免疫状态下所成的瘤性质有差异

Tumors in immunocompetent mice are qualitatively different from tumors in immunodeficient mice 不同免疫状态下所成的瘤性质有差异 Primary tumor growing in: Tumor cell line Inject into naive WT recipients Monitor tumor growth Growth profile Immunocompetent Mouse 免疫正常小鼠 Immunodeficient Mouse 免疫缺陷小鼠 Edited progressor Unedited progressor Unedited regressor Immunocompetent Mouse 免疫正常小鼠

Inn atdolpbimermibnunity Macrophage B cell Tcell 巨噬细胞 Dentritic cell /o Natural killer cell 树突状细胞包 自然杀代 Basophil Mast carbody 嗜碱性粒细胞 肥大痴 Eosinophil 嗜配胞 Neutrophil Cat中性細跑

Innate Immunity Basophil 嗜碱性粒细胞 Eosinophil 嗜酸性粒细胞 Neutrophil 中性粒细胞 Macrophage 巨噬细胞 Natural killer cell 自然杀伤细胞 Dentritic cell 树突状细胞 Mast cell 肥大细胞 B cell T cell CD4+ T cell CD8+ T cell Adoptive Immunity Antibody 抗体

Innate Immunity Dentritic cell 树突状细胞 Phagocytosis various stress-induced 吞噬作用 genes“应急反应基因” Tumor cell 肿瘤细胞 Natural killer cell 自然杀伤细胞 Tumor-cell peptides 肿瘤细胞相关多肽 Macrophage 巨噬细胞 Heat-shock proteins O热休克蛋白

Innate Immunity Natural killer cell 自然杀伤细胞 Dentritic cell 树突状细胞 Macrophage 巨噬细胞 Tumor cell 肿瘤细胞 Tumor-cell peptides 肿瘤细胞相关多肽 Heat-shock proteins 热休克蛋白 Phagocytosis various stress-induced 吞噬作用 genes “应急反应基因

Adoptive Immunity Lymph node Dying tumor cell 淋巴结 死亡的肿瘤细胞 APC (antigen B cell presentating cell 抗原提呈细胞 T cell CD4+T cell CD8+ T cell T cell NK cell

Adoptive Immunity CD4+ T cell CD8+ T cell T cell APC （antugen presentating cells） 抗原提呈细胞 B cell Dying tumor cell 死亡的肿瘤细胞 Lymph node 淋巴结 T cell NK cell