1. Dr. Gülderen Yanıkkaya Demirel
TUMOR IMMUNOLOGY
Dr. Gülderen Yanıkkaya Demirel

2. WHAT YOU WILL LEARN Cancer stem cell Tumor Immunity Tumor Antigens
Tumor Cell Escape Mechanisms
Immunosurveillance/Immunoediting

3. CANCER STEM CELL
Ikehara S, J of Hematotherapy & SC Research, 12: , 2003

4. EVIDENCE for TUMOR IMMUNITY
Spontaneous regression
Regression of metastases after removal of primary tumor
Infiltrations of tumors by lymphocytes and macrophages
Lymphocyte proliferation in draining lymph nodes
Increased cancer risk after immunosuppression and immunodeficiency

5. IMMUNODEFICIENCY and TUMOR

6. IMMUNOGENECITY of TUMORS

7. TUMOR IMMUNOLOGY

8. TUMOR ANTIGENS mutations abnormal expression oncogenic viruses
oncofetal antigens
altered surface modifications
tissue specific differentiation antigens

9. BCR/ABL

10. Origin of tumor antigens
Figure part 1 of 2

11. Figure part 2 of 2

14. Figure part 1 of 2

15. Figure 14-17

16. IMMUNE RESPONSES TO TUMORS
Innate immune responses
NK cells
Macrophages
Innate like cells
Adaptive immune responses
T cells
Antibodies

17. IMMUNOSURVEILLANCE
An hypothesis that states that a physiologic function of the immune system is to recognize and destroy malignantly transformed cells before they grow into tumors.
Proposed by Paul Ehrlich, Macfarlane Burnet and Lewis Thomas
Implies that cells of the immune system recognize something “foreign” on transformed/tumor cells.

18. IMMUNOSURVEILLANCE & IMMUNOEDITING
No disease
Preneoplasia
Disease

19. IMMUNE MODIFIERS
Cytokines requiring host participation: aldesleukin [interleukin (IL)-2] and IFN a 2;
Antibodies requiring host participation—to the extent that they invoke antibody dependent cellular cytotoxicity for optimal efficacy: alemtuzumab, tositumomab, cetuximab, ibritumomab, rituximab, and trastuzumab;
Immunostimulants known to require host participation: Bacillus Calmette-Guerin, levamisole, and imiquimod;
Immunostimulants with unknown host participation: lenalidomide and thalidomide

22. RESIDUAL DISEASE
Reya, T., et al. Nature, 2001

23. Cancer immunotherapy with mRNA transfected dendritic cells - A personalized form of cell therapy
Antigen Loading
(mRNA transfection)
GM-CSF, IL-4
Immature DC
Monocytes
DC maturation
IL-1b, IL-6, TNF-a, PGE2
Tumor antigens
(mRNA)
Antigen-Loaded
Mature DC
Cryopreserved
DC Vaccine
Tumor Biopsy
Leukapheresis

26. POTENTIAL CYTOTOXIC MECHANISMS of ANTI TUMOR ANTIBODIES

27. INDUCTION of ANTI TUMOR RESPONSE

28. LAK (Lymphokine Activated Killer) CELLS

29. SUMMARY 1) Immunological recognition of tumor occurs.
2) Tumors emerge in individuals who have overcame the immunological surveillance.
3) Evasion mechanisms include reduced tumor antigen presentation and local immunoregulatory factors: inhibitory cytokines and cells.
4) Reversal of tolerogenic response is goal of immunotherapy
Passive immunization (antitumor antibodies, adoptive T cell therapy).
Active immunization (vaccine=antigen plus adjuvant).
The goal is to induce antigen specific effector T cells while eliminating regulatory negative immunoregulatory pathways