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Tumor Immunology

Tumor Immunology. Wirsma Arif Harahap Surgical Oncologist Surgery Department Andalas Medical School. Immune System. A complex of lymphoid organs highly specialized cells circulatory system separate from blood vessels. Immune System.

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Tumor Immunology

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  1. Tumor Immunology WirsmaArifHarahap Surgical Oncologist Surgery Department Andalas Medical School

  2. Immune System A complex of lymphoid organs highly specialized cells circulatory system separate from blood vessels

  3. Immune System Lymphatic vessels form a circulatory system that operates in close partnership with blood circulation Carries lymph, a fluid that contains WBCs (chiefly lymphocytes) Lymph nodes provide “meeting grounds”

  4. Four Primary Functions Recognition of self self-tolerance immunological privilege Immunosurveillance Intracellular hormones Defense against infection

  5. Role of the immune system is to protect from: Virus Influenza Polio mellitus Parasites Tapeworms Malaria Helminths Fungi Candida albicans Bacteria Tubercule bacillus Staphylococci

  6. Dendritic cell Origin of cells involved in the immune response Myeloid progenitor Haemopoietic stem cell Monocyte Lymphocyte progenitor Macrophage Basophil Neutrophil B cell Thymus NK cell Mast cell Eosinophil CD8 T cell CD4 T cell Plasma cell

  7. 3 Types of Actions of the Immune System Mechanical Non-specific (innate immunity) Specific ( adaptive immunity )

  8. Overview of immune responses

  9. Interactions between innate and& adaptive immunity 1. Innate immunity => Ag presentation (by Dendritic cells) 2. Adaptive immunity => Ag recognition (by T & B lymphocytes)

  10. Evidence for the role of immune system in tumor rejection • Spontaneous regression • Infiltration of tumors by lymphocytes and macrophages • Regression of metastases after removal of primary tumor • Regression after chemotherapy • Lymphocyte proliferation in draining lymph nodes • Higher incidence of cancer after immunosuppression/immunodeficiency (AIDS, neonates, aged, transplant patients)

  11. cause of immuno-deficiency malignancy • primary (inherited) immunodeficiency lymphomas lymphoma, cervical cancer, liver cancer, skin cancer, Kaposi’s sarcoma. • secondary (acquired) immunodeficiency • malaria Burkitt’s lymphoma • autoimmunity lymphoma Association between immunodeficiency and cancer

  12. Tumors stimulate an immune response • Animals can be immunized against tumors • Immunity is transferable from immune to naïve animals • Tumor specific antibodies and cell have been detected in humans with some malignancies

  13. Etiology Of Tumor 1) Inherited : Expression of inherited oncogene e.g. viral gene incorporated into host gene 2) Viral: - Human papilloma, herpes type 2, HBV, EBV (DNA) - Human T-cell leuckemia virus (RNA) 3) Chemical: - Poly cyclic hydrocarbons cause sarcomas - Aromatic amines cause mammary carcinoma - Alkyl nitroso amines cause hepatoma 4) Radiological: Ultraviolet & ionizing irradiation 5) Spontaneous: failure in the cellular growth control

  14. Tumor Associated Antigens !) Viral Antigen : a- Viral proteins and glycoproteins b- New antigens produced by virally infected host cells under control of viral nucleic acid 2) Tumor specific antigens : - Tumor cells develop new antigen specific to their carcinogens 3) Tumor specific transplantation antigens : - Tumor cells express new MHC antigens due to alteration of normally present MHC antigens

  15. Tumor Associated Antigens 4) Oncofetal antigens: a- Carcino-embryonic antigens (CEA) - Normally expressed during fetal life on fetal gut - Reappearance in adult life: GIT, pancreas, biliary system and cancer breast b- Alpha fetoprotein: - Normally expressed in fetal life - Reappearance in adult life; hepatoma

  16. Immunity against tumor All components, specific and nonspecific, humoral and cellular affect tumor progression and growth

  17. Antigens expressed on tumor cells Major Histocompatability Complex antigens TSTA Tumor-specific transplantation Ag TATA Tumor-associated transplantation Ag TSTA: unique to a tumor Play an important role in tumor rejection. TATA : shared by normal and tumor cells Tumor-associated developmental Ag (TADA) Tumor-associated viral Ag (TAVA)

  18. Tumor associated transplantation antigens: shared Ag on virally induced tumors

  19. Discovery of tumor specific transplantation antigens, TSTA

  20. Tumor-Associated Developmental Ags • Found on cancer cells and on fetal cells. • Do not trigger anti-tumor immunity. • Used in diagnosis. • Alpha-fetoprotein(AFP) Cancers of liver • Carcinoembryonic Ag (CEA) colorectal cancer • Breast cancer  CA 15-3 • Ovarial cancer  CA 15-5

  21. Escape from immunosurveillance Lack of Neo-antigens

  22. Escape from immunosurveillance Lack of Neo-antigens

  23. Escape from immunosurveillance Lack of class I MHC

  24. Escape from immunosurveillance Tumors secrete Immunosuppressive molecules

  25. Escape from immunosurveillance Tumors shed their neo-antigens

  26. tumor Class I MHC B7 CD28 tumor Ag CTL • Tumors may fail to express costimulatory molecules involved in T cell activation. Tumors escape the action of CTL by not expressing B7 which provides 2nd signal involved in T cell activation

  27. Utility of Immunology in Cancer Treatment

  28. Use of tumor associated antigens • Raise monoclonal antibodies • Use antibodies for diagnosis • Use antibodies for therapy • Stimulate the in vivo specific response • Specific active treatment • Specific passive treatment • Adjuvant therapy to augment specific immunity

  29. Use of tumor associated antigensmonoclonal antibodies

  30. Monoclonal antibodies:use as a diagnostic tool

  31. killed tumor cells, purified or recombinant Ag specific non- specific BCG, Propionibacterium acne, levamisole, etc. non-specific LAK cells, cytokines antibodies alone or conjugated with other agent, activated T cells specific Immunotherapy of tumors active immunotherapy passive immunotherapy

  32. Non-specific immunotherapy bacterial products BCG, P. acnes, muramyl dipeptide activate macrophages and NK cells (via cytokines) synthetic molecules pyran, poly I:C interferon production cytokines IFN-, IFN-, IFN-, IL-2, TNF- activate macrophages and NK cells

  33. remission of hairy cell leukemia, weak effect on carcinomas increased expression of class-I MHC, possible anti tumor effect IFN increased expression of class-I MHC, Tc and NK cell activation IFN remission of ovarian carcinoma T cell proliferation and activation, NK cell activation remission in renal cell carcinoma and melanoma IL-2 macrophage and lymphocyte activation reduction in malignant ascites TNF Cytokine immunotherapy

  34. Active Immunization: The host actively elicits an immune response. • Specific • Vaccination with viral Ags: e.g. • Hepatitis B virus • Human Papilloma virus (HPV)

  35. Thank You

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