Chapter 20 Tumor Immunology

1. Chapter 20 Tumor Immunology

3. Contents • PartⅠ Introduction • PartⅡ Tumor antigens • PartⅢ Immune response to tumors • PartⅣ Mechanism of tumor escape from immune surveillance • PartⅤ Immunotherapy of tumors

4. PartⅠ Introduction • Tumor immunology tumor immunology is the study of ①the antigenic properties of tumor cells, ②the host immune response to these tumor cells, ③the immunological consequence of malignant cells growth to the host, ④and the means by which the immune system can be modulated to recognize tumor cells and promote tumor eradication. • Immunosurveillance

7. PartⅡ Tumor antigens By their patterns of expression: • Tumor specific antigen (TSA) • Tumor associated antigens (TAA)

8. Tumor specific antigen (TSA) Antigens that are only expressed on tumor cells but not on normal cells. high specificity. tumor-specific transplantation antigens (TSTA)

9. tumor-specific transplantation antigens (TSTA) MCA(甲基胆蒽)

11. Tumor associated antigens (TAA) Antigens that are also expressed on normal cells, but high expressed on tumor cells. Without tumor specificity: CEA, AFP

12. Common tumor antigens • ①Embryonic antigens • ②Tumor antigens induced by virus • ③Mutated oncogene or suppressor oncogene encoded protein • ④Overexpressed cellular proteins

13. ①Embryonic antigens • AFP (alpha fetoproein) • Normal<20 ng/ml • Hepatocarcinoma> 500ng/ml • CEA (carcinoembryonic antigen ) • Normal<20 ng/ml • colon carcinoma: 5-10 times higher

14. Carcinoembryonic antigen:clinical application

15. ②Tumor antigens encoded by genomes of oncogenic viruses: • HBV------ liver cancer • HPV------ cervical carcinoma • EBV------ B cell lymphoma and nasopharyngeal carcinoma

16. Virus induced tumor antigen

17. ③Products of mutated genes: • Some tumor antigens are produced by mutated oncogenes and tumor suppressor genes: Ras, p53

18. ④Overexpressed cellular proteins and abnormally expressed proteins: • gp100, MAGE in melanomas • Cancer-testis antigens

19. Part Ⅲ Immune response to tumors T cells: αβT, γδT NK cells • Cellular immunity Macrophages Dendritic cells • Humoral immunity

20. (1)T lymphocytes: ①The principal mechanism of tumor immunity is killing of tumor cells by CTL Tumor antigens DC cross presentation CD8+T （CTL）

25. ② CD4+T cells: secret cytokines

26. ③γδT cells: -Not restricted by MHC - Kill cells that could escape from NK cells

27. (2)NK cells: NK cells kill many types of tumor cells, especially cells that have reduced class I MHC expression and can escape killing by CTL.

28. activated Tumor cell

29. (3) Macrophages: ① APC ② release of lysosomal enzymes, reactive oxygen intermediates, nitric oxide ③ ADCC ④ secrete cytokines (4)Dendritic cells: ① APC------Induce adaptive immune response ② Inhibit tumor growth directly

31. (5) Antibodies:① Activating complement ② ADCC③ Opsonization

32. Antitumor Effect CMI NK cell Tumor cell Humoral Mechanisms Macrophage Kumar et al. Basic Pathology 6th ed. Figure 6-32

33. PartⅣ Mechanism of tumor escape from immune surveillance ①Tumor antigens can’t elicit immune responses ------poor antigenicity and antigenic modulation. ②Tumor antigens may be sheltered or blocked. ③Class I MHC expression may be down-regulated on tumor cells so that they can not be recognized by CTL. ④Tumors may fail to induce CTL because most tumor cells do not express costimulators. ⑤Tumors secrete Immunosuppressive factors. ⑥Tumor cells induced apoptosis

34. ①Tumor antigens can’t elicit immune responses ------poor antigenicity and antigenic modulation.

35. ②Tumor antigens may be sheltered or blocked. The cancer cells that have the altered self-peptide are recognized and killed A mutation occurs that stops expression of the peptide and now the cells are no longer recognized.

36. ③Class I MHC expression may be down-regulated on tumor cells so that they can not be recognized by CTL.

37. ④Tumors may fail to induce CTL because most tumor cells do not express costimulators.

38. ⑤Tumors secrete Immunosuppressive factors.

39. ⑥Tumor cells induced apoptosis.

40. Factors related to host: • Poor immune function • Tumor inhibit immune function of host

41. PartⅤ Immunotherapy of tumors • Active immunotherapy • Target immunotherapy • Adoptive immunotherapy • Cytokine therapy • Gene therapy

42. Active immunotherapy Stimulation of active host immune responses to tumors: • Vaccination with tumor cells , tumor antigens, or with APC.

45. Target immunotherapy

46. Adoptive immunotherapy • LAK (lymphokine activated killer) • TIL (tumor infiltrating lymphocyte) • CD3AK(CD3 antibody activated killer) • CTL (cytotoxic T lymphocyte)

48. Cytokine therapy

49. Gene therapy