2. A fight between immune cells and cancer But, sometimes we lose

6. Cell Growth Control of cell growth Growth-promoting Proto-oncogenes Growth-restricting Tumor-suppressor genes

8. Discovery of Immune surveillance of tumors 1. Immune Surveillance- Macfarlane Burnet in 1950s 2. Use syngeneic mouse strain => Transplantation exp 3 . Immunization w/ irradiated tumor X cells protects a syngeneic mouse w/ live X tumor cells but not Y tumor cells. 4 . Antigens expressed by tumors, termed tumor antigens. 5. Defense against tumors is mainly mediated by T cells

9. Key Concepts in Tumor immunity 1. Tumors express Ags that are recognized as foreign by the host immune system. 2. Immune responses frequently fail to prevent the growth of tumors. 3. The immune system can be activated by external stimuli to effectively kill tumor cells and eradicate tumors. 4. Various strategies have been developing to enhance the anti-tumor immune responses.

11. Examples of tumor antigens -I

12. Examples of tumor antigens -II

13. Tumor antigens arise by point mutations in self proteins

14. Tumor antigens arise by reactivated genes or overexpressed genes

15. Immune responses to tumors 1. Adaptive immune responses to tumors: a. CD8 CTLs are the key players on the killing effect of tumors. b. CD4 T helper cells => cytokines => CTLs c. Abs => activating complements or Ab-dep cell-med toxicity => preventing oncogenic viruses 2. Innate immune responses to tumors: a. NK cells kill many types of tumor cells that have reduced class-I but express ligands for activating NK cells. b. Macrophages => Ab-med phagocytosis => Cytokines (TNF-a), ROS, & NO

16. I nduction of T cell responses to tumor s Cross-priming (cross-presentation) mediated by APCs, ex. DCs

17. Direct CTL / NK attack TUMOUR CELL Fas (CD95) FasL TCR Class I + Ag Perforin Granzyme B CTL

18. Antigen-specific tumor killing: B cells (opsinization & ADCC) Tumor Complement Macrophage/ opsinization FcR Fab Fc NK cells & ADCC sIg Tumor

19. Antigen-specific Tumor Killing: T Cells MHCI peptide Apoptosis T cell receptor (TCR) Tumor IFN-  Granzyme B CD8

21. Tumor and activated T cells Two major pathways for TCL: Fas-mediated and perforrin-mediated

22. Mechanisms of Tumor evasion Tumors w/Fas Treg infiltrating

26. Three Es of Immunoediting CTL CTL NKT NK CD4 NK CTL CD4 NK CTL Elimination Equilibrium Escape Genetic instability / tumour heterogeneity

27. Immunoediting of Cancer

29. How does MM evade the immune response? myeloma cancer cell Broken up to release antigens APC APC recruits CTL specific for myeloma Ag T T T T T T cells recognise and destroy other cancer cells MM cell release factors which ‘turn off’ T cells

31. Tumor vaccines-Targeting DCs

32. Types of Tumor Vaccines

33. Immunotherapy with cytokine gene-transfected tumor cells

34. Systemic cytokine therapy for tumors

35. Passive Immunotherapy for tumors Adoptive cellular therapy

36. Therapy with Anti-tumor Monoclonal Abs

37. Approved Anti-tumor mAb

38. SUMMARY 1. Cancer is a complex and progressive genetic disease. 2. Tumors express Ags that could be recognized by the immune system. But some tumors are weakly immunogenic and the immune system often fails to eradicate them. 3. Cancer from clinical cases usually represents the leading of cancer development over the anti-cancer immune responses. 4. The imperative issue in the field of tumor immunology is to improve the capability of immune defenses to fight cancer.