免疫学课件2015 肿瘤免疫20150416.20150417

DEPARTMENT OF IMMUNOLOGYImmunity to tumorsDEPARTMENT OF IMMUNOLOGYContent 1.General Features 1.General Features 2.Tumor antigen2.Tumor antigen3.Immune Responses3.Immune Responses4.Evasion of Immune Responses4.Evasion of Immune Responses5.Immunotherapy5.ImmunotherapyDEPARTMENT OF IMMUNOLOGY Cancer is a major health problem worldwide and one of the most important causes of morbidity and mortality in children and adults.DEPARTMENT OF IMMUNOLOGYRobin BushThe sister of George W.Bush,die from leukemia,at the age of 4.Walt DisneyThis famous animator,producer and co-founder ofthe corporation known as The Walt Disney Company died at the age of 65 from lung cancer,making him one of the most famous celebritiesto have died from smoking.Paul NewmanPaul Newman was of course a great actor,but was known well for his healthy line of food.He struggled with lung cancer,and passed awayon September 26,2008,at the age of 83.DEPARTMENT OF IMMUNOLOGYGeneral Features vTumor express antigens that are recognized as foreign by the immune system of the tumor-bearing host.vImmune responses frequently fail to prevent the growth of tumors.vThe immune system can be activated by external stimuli to effectively kill tumor cells and eradicate tumors.DEPARTMENT OF IMMUNOLOGYTumor Antigen DEPARTMENT OF IMMUNOLOGYvImmune responses frequently fail to prevent the growth of tumorsvFirst,tumor cells are derived from host cells.vSecond,the rapid growth and spread of tumors vThird,specialized mechanisms for evading host immune responses.DEPARTMENT OF IMMUNOLOGYvThe immune system can be activated by external stimuli to effectively kill tumor cells and eradicate tumors.-Active immunotherapy;-Passive immunotherapy.DEPARTMENT OF IMMUNOLOGYSteven A.Rosenberg Steven A.Rosenberg is a leading cancer researcher and surgeon.He is credited with developing the use of IL-2 and immune cells for the treatment of patients with melanoma in a procedure termed adoptive cell transfer.LAKTILIL-2TCR gene transfer Combination with chemotherapyActivated immune cell adoptive Transfer for tumor therapyDEPARTMENT OF IMMUNOLOGYDEPARTMENT OF IMMUNOLOGYContent 1.General Features 1.General Features 2.Tumor antigen2.Tumor antigen3.Immune Responses3.Immune Responses4.Evasion of Immune Responses4.Evasion of Immune Responses5.Immunotherapy5.ImmunotherapyDEPARTMENT OF IMMUNOLOGYTumor Antigen The earliest classification:vTumor-specific antigenvTumor-associated antigenDEPARTMENT OF IMMUNOLOGYTumor Antigen vTumor-specific antigen Antigen that are expressed on tumor cells but not on normal cells were called tumor-specific antigens;some of these antigens are unique to individual tumors,whereas others are shared among tumors of the same type.DEPARTMENT OF IMMUNOLOGYTumor Antigen vTumor-associated antigen Tumor antigens that are also expressed on normal cells were called tumor-associated antigens;in most cases,these antigens are normal cellular constituents whose expression is aberrant or dysregulated in tumorsDEPARTMENT OF IMMUNOLOGYTumor Antigen DEPARTMENT OF IMMUNOLOGYTumor Antigen The modern classification relies on the molecular structure and source of the antigenDEPARTMENT OF IMMUNOLOGYTumor Antigen DEPARTMENT OF IMMUNOLOGYTumor Antigen Type of antigenExamples of human tumor antigensProducts of oncogenes,tumor suppressor genesOncogenes:Ras mutations(10%of human carcinomas),p210 product of Bcr/Abl rearrangements(CML),overexpressed Her-2/neu(breast and other carcinomas)Tumor supressor genes:mutated p53(present in 50%of human tumors)Mutants of cellular genes not involved in tumorigenesisp91A mutation in mutagenized murine mastocytoma;various mutated proteins in melanomas recognized by CTLsProducts of genes that are silent in most normal tissuesCancer/testis antigens expressed in melanomas and many carcinomas;normally expressed mainly in the testis and placentaProducts of overexpressed genesTyrosinase,gp100,MART in melanomas(normally expressed in melanocytes)Products of oncogenic virusesPapillomavirus E6 and E7 proteins(cervical carcinomas)EBNA-1 protein of EBV(EBV-associated lymphomas,nasopharyngeal carcinoma)SV40 T antigen(SV40-induced rodent tumors)Oncofetal antigensCarcinoembryonic antigen(CEA)on many tumors,also expressed in liver and other tissues during inflammationAlpha-fetoprotein(AFP)Glycolipids and glycoproteinsGM2 GD2 on melanomasDifferentiation antigens normally present in tissue of originProstate-specific antigenMarkers of lymphocytes:CD10,CD20,Ig idiotypes on B cellsDEPARTMENT OF IMMUNOLOGYContent 1.General Features 1.General Features 2.Tumor antigen2.Tumor antigen3.Immune Responses3.Immune Responses4.Evasion of Immune Responses4.Evasion of Immune Responses5.Immunotherapy5.ImmunotherapyDEPARTMENT OF IMMUNOLOGYImmune Responses to TumorsvT lymphocytesvAntibodiesvNK cellsvMacrophagesDEPARTMENT OF IMMUNOLOGYImmune Responses to TumorsvT lymphocytes The killing of tumor cells by CD8+CTLDEPARTMENT OF IMMUNOLOGYImmune Responses to TumorsvT lymphocytesDEPARTMENT OF IMMUNOLOGYDEPARTMENT