医学免疫学资料：Chapter25 tumor immunology

1、Chapter25 Tumor Immunology。 Part Introduction Part Tumor antigens Part Immune response to tumors Part Mechanism of tumor escape from immune surveillance Part Immunotherapy of tumorsPart Introduction Tumor immunology；Immunosurveillance Tumors express antigens that are recognized as foreign by the imm

2、une system of the tumor-bearing host. Immune response frequently fail to prevent the growth of tumors. The immune system can be activated by external stimuli to effectively kill tumor cells and eradicate tumors.By their patterns of expression: Tumor specific antigen (TSA)：Antigens that are only expr

3、essed on tumor cells but not on normal cells. high specificity. tumor-specific transplantation antigens (TSTA) Tumor associated antigens (TAA) ：Antigens that are also expressed on normal cells, but high expressed on tumor cells. Without tumor specificity: CEA, AFPTumor specific antigen: Antigens ind

4、uced by chemical carcinogen or physical factors (X-ray): P815, Meth A Tumor antigens encoded by genomes of oncogenic virusesCommon tumor antigens： Embryonic antigens；Tumor antigens induced by virus；Mutated oncogene or suppressor gene coded protein Overexpressed cellular proteinsOncofetal antigens: O

5、ncofetal antigens are proteins that are expressed at high levels on cancer cells and in normal developing fetal but not adult tissues. As techniques for detecting these antigens have improved, it has become clear that their expression on adults is not limited to tumors. Their main importance is that

6、 they provide markers that aid in tumor diagnosis. Carcinoembryonic antigen (CEA) and alpha-fetoprotein(AFP )CEA: High CEA expression is normally restricted to cells in the gut, pancreas, and liver during the first two trimesters of gestation, and low expression is seen in normal adult. CEA expressi

7、on is increased in many carcinomas of the colon, pancreas, stomach, and breast, and serum levels are increased in these patients. The level of serum CEA is used to monitor the persistence or recurrence of the tumors after treatment. The usefulness of CEA as a diagnostic marker for cancer is limited

8、by the fact that serum CEA can also be elevated in the setting of non-neoplastic diseases, such as chronic inflammatory conditions of the bowel or liver.AFP: AFP is a circulating glycoprotein normally synthesized and secreted in fetal life by the yolk sac and liver. Serum levels of AFP can be signif

9、icantly elevated in patients with hepatocellular carcinoma and germ cell tumor. An elevated serum AFP level is useful indicator of advanced liver or germ cell tumors or of recurrence of these tumors after treatment. The diagnostic value of AFP as a tumor marker is limited by the fact that elevated s

10、erum levels are also found in non-neoplastic diseases, such as cirrhosis of the liver.Tumor antigens encoded by genomes of oncogenic viruses: HBV- liver cancer；HPV- cervical carcinoma；EBV- B cell lymphoma and nasopharyngeal carcinoma Products of mutated genes: Some tumor antigens are produced by mut

11、ated oncogenes and tumor suppressor genes: Ras, p53 Tumor antigens may be produced by other mutated genes. Some patients with cancer have circulating CD4+ and CD8+T cells that can respond to the products of mutated genes such as Ras and P53. Furthermore, in animals, immunization with mutated Ras or

12、P53 proteins induces CTLs and rejection responses against tumors expressing these mutants.Overexpressed cellular proteins and abnormally expressed proteins: MAGE in melanomas；Cancer-testis antigensPart Immune response to tumorsl Cellular immunity： T cells: T, T；NK cells；macrophages；dendritic cells H

13、umoral immunity T lymphocytes:The principal mechanism of tumor immunity is killing of tumor cells by CTLCD4+T cells；T cellsNK cells: NK cells kill many types of tumor cells, especially cells that have reduced class I MHC expression and can escape killing by CTL Macrophages: Mechanisms include the re

14、lease of lysosomal enzymes, reactive oxygen intermediates, nitric oxide and cytokines. Dendritic cells: Induce adaptive immune response；Inhibit tumor growth directly Antibodies: Activating complement； ADCC； OpsonizationPart Mechanism of tumor escape from immune surveillance Factors related tumor: Tu

15、mors lose expression of antigens that elicit immune responses. Tumor antigens may be blocked. Class I MHC expression may be down-regulated on tumor cells so that they can not be recognized by CTL. Tumors may fail to induce CTL because most tumor cells do not express costimulators. The products of tu

16、mor cells may suppress anti-tumor immune responses.Factors related to host: Poor immune function；Tumor inhibit immune function of hostPart Immunotherapy of tumors Active immunotherapy Target immunotherapy Adoptive immunotherapy Cytokine therapy Gene therapyStimulation of active host immune responses

17、 to tumors: Vaccination with tumor cells and tumor antigens, or with APC. Augmentation of host immunity to tumors with cytokines and costimulators Nonspecific stimulation of the immune system:BCGCytokine： Cytokines may also be administered systemically for the treatment of human tumors. IL-2 works b

18、y stimulating the proliferation and anti-tumor activity of NK cells and CTLs. IFN-a works by increasing the cytolytic activity of NK cells and class I MHC expression on various cell types. Their side effects limited this treatment.Nonspecific stimulation of the immune system: The BCG mycobacteria activate macrophages and thereby promote macrophage-mediated