胸外科和免疫学的结合课件.pptx

1、胸胸外科和免疫学的结合外科和免疫学的结合Immunology and Thoracic SurgeryDavid B Skinner,M.D.,Tom R.DeMeester,M.D.Vol.21(5),May 1976ABSTRACT This report reviews the current status of three types of diseases in which knowledge of immunology is changing the practice of thoracic surgery.Immunotherapy of several types is cur

2、rently being investigated experimentally and clinically and promises to change therapy for bronchogenic and esophageal neoplasms.先天性和获得性免疫系统肺部的免疫系统The alveoli.in mouse and man are comprised almost entirely of alveolar macrophages.这些巨噬细胞分泌大量的具有抗微生物作用的因子，同时还具备抗原呈递功能从而引发抗原特异性免疫反应Are there any other imm

3、une cells in the lungs?Dendritic cells are known to project their dendrites into the airway lumen.T cells(predominantly cytotoxic)exist between epithelial cells.Some neutrophils and rare mast cells*上皮细胞本身也参与了肺部免疫反应，因为上皮细胞可以分泌趋化因子，细胞因子，抗微生物复合物。l理论的提出：Ehrlich P.1909；Burnet FM.1957;1964l争议：Nude mice an

4、d thymectomized micel实验和临床证明:各种免疫相关分子基因缺陷动物模型的建立；器官移植患者，HIV 感染病人l理论的进一步改进和发展肿瘤免疫监视(Immunosurveillance)理论的发展历程肿瘤免疫编辑理论Elimination,Equilibrium,and EscapeImmunity,Vol.21,137148,2004 Dunn,D.P.et al.肿瘤免疫逃逸T 细胞 耐受，衰竭，老化肿瘤免疫治疗如何阻断或去除抑制免疫功能的如何阻断或去除抑制免疫功能的因素因素如何如何mimic有效的抗微生物免疫反应来调节抗肿瘤免疫反应有效的抗微生物免疫反应来调节抗肿瘤免疫

5、反应 Types of immunotherapy(lung cancer):Cancer vaccinesMonoclonal antibodiesChimeric antigen receptors-T cell immunotherapy(CAR)Checkpoint immunotherapy:PD1,PDL1,CTLA-4 Li,L.et al.R E S E A R C H A R T I C L E I M M U N O L O G Y Selective Effects of PD-1 on Akt and Ras Pathways Regulate Molecular Co

6、mponents of the Cell Cycle and Inhibit T Cell ProliferationPD-1 inhibits activation of CDK2Patsoukis,N.et al.PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation NATURE COMMUNICATIONS|2015Patsoukis,N.et al.Metabolic Competition in the T

7、umor Microenvironment Is a Driver of Cancer ProgressionVolume 162,Issue 6,10 September 2015Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor GrowthVolume 162,Issue 6,10 September 2015样样本本库库建立建立 A研究思路研究思路PD1 抗体治疗肿瘤的可能机制和新的免疫治疗方案lReinvigorating exhausted T cells(proliferation capacity/effector function)lAlternation the properties of cancer cellslManipulation of p27kip1肺癌生物样本库的建立和肿瘤免疫研究思路 B男性女性鳞癌腺癌病例数鳞癌腺癌41%59%373255EGFR基因突变和靶向治疗获得性耐药机制与免疫学的相关性 OncoImmunology 1:1,71-74;2012胸外科影像学影像学分子生物学分子生物学免疫学免疫学研究研究生存期无疾病进展期免疫治疗靶向治疗化疗放疗精精准准+全局全局