Tumor immunity

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Tumor immunity

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Tumor immunity

  1. 1. Tumor Immunity basics Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Tumor • Cells that continue to replicate, f Cells that continue to replicate, fail to differentiate into specialized cells, and become immortal. 1. Malignant: A tumor that grows indefinitely and spreads (metastasis)--also called cancer: kills host 2. Benign: A tumor that is not capable of metastasis: does not kill host muscle, nerve, bone, blood
  3. 3. Types of Cancer • Carcinoma: arising from epithelial tissue, such as glands, breast, skin, and linings of the urogenital, digestive, and respiratory systems (89.3% of all cancers) • Sarcoma: solid tumors of muscles, bone, and cartilage that arise from the embryological mesoderm (1.9% of all cancers) • Leukemia: disease of bone marrow causing excessive production of leukocytes (3.4% of all cancers) • Lymphoma, Myeloma: diseases of the lymph nodes and spleen that cause excessive production of lymphocytes (5.4% of cancers) Dr.T.V.Rao MD 3
  4. 4. Etiology of Cancer 1. Genetic factors: mutations, translocation, amplifications 2. Environmental factors: UV, chemicals, viral infections • Conversion of proto-oncogenes (potential for cell transformation) to oncogenes (cell transformation) alteration in tumor suppressor genes Dr.T.V.Rao MD 4
  5. 5. Tumour Antigens • When a cell undergoes malignant transformation it acquires new surface antigens and may loose some normal antigens • A malignant tumour antigenically different from normal tissues of the host it is considered as an allograft and expected to induce immune response. Dr.T.V.Rao MD 5
  6. 6. Tumour Antigens • Antigens that are present in the tumour cells but absent in the corresponding normal cell of the host are known as tumour antigens • Two types – tumour specific and tumour associated antigens Dr.T.V.Rao MD 6
  7. 7. Tumour specific antigens • These are antigens present on the membrances of the malignant cells and induce an immune response when the tumour is transplanted in syngenic animals • TATA Tumour associated transplantation antigens • TSTA Tumour specific transplantation antigens Dr.T.V.Rao MD 7
  8. 8. Tumour associated antigens • These are foetal antigens that are present in embryonic and malignant cells but not in the adult normal cells. • Examples – • Alpha fetoproteins in hepatoma and carcinoembronic antigen in the colonic cancer Dr.T.V.Rao MD 8
  9. 9. Evidence to tumour Immunity • High frequency in cancers in immunosuppressed patients Papilloma virus driven cervical cancer • AIDS lymph reticular malignancies • Immunosuppressive therapy Dr.T.V.Rao MD 9
  10. 10. Tumor killing Non-specific: NK cells, T cells (NKG2D), macrophages, NK T cells Antigen-specific: Antibody (ADCC, opsinization); T cells (cytokines, Fas-L, perforin/granzyme) Dr.T.V.Rao MD 10
  11. 11. Immune Response in Malignancy • T cell mediated immunity • Lymhokines helps in destruction of tumour cells • Humoral response is beneficial Dr.T.V.Rao MD 11
  12. 12. Virally-induced Cancers DNA viruses: papova (papilloma, SV40), hepatitis, EBV RNA viruses: retroviruses---> Human Tlymphotropic viruses (HTLV-I and HTLV-II) cause T cell leukemia Hepatitis C viral Infection Dr.T.V.Rao MD 12
  13. 13. Immunological surveillance • In 1970 Burnet proposed that malignant cells arise by somatic mutation and the immune system keeps a constant vigilance on these cells and destroy them • Fast rate of growth of malignant cells Dr.T.V.Rao MD 13
  14. 14. Evidence for Tumor Immunity • Spontaneous regression: melanoma, lymphoma • Regression of metastases after removal of primary tumor: pulmonary metastases from renal carcinoma • Infiltration of tumors by lymphocytes and macrophages: melanoma and breast cancer • Higher incidence of cancer after immunosuppression, immunodeficiency (AIDS, neonates), aging, etc. Dr.T.V.Rao MD 14
  15. 15. Immunotherapy of Cancer • Non specific active immune therapy employs BCG • BCG evokes tumour immunity enhancing macrophage cytotoxicity • Levamisole Dr.T.V.Rao MD 15
  16. 16. Specific Immunotherapy • Monoclonal antibodies to tumour antigens • Lymhokines activated killer cells obtained by treatment of natural killer cells with interleukin used in renal carcinoma Dr.T.V.Rao MD 16
  17. 17. Summary • Both genetic and environmental factors are involved in tumor formation • Immune system plays a surveillance role in controlling the development of cancer, however, it also induces epigenetic changes in tumors that result in cancer (immune editing) Dr.T.V.Rao MD 17
  18. 18. Summary ( Contd) • Altered expression of antigens by tumors (mutation, viral antigens, cryptic epitopes), expression of costimulatory molecules in tumors, or cross-presentation of tumor antigens by APC results in the immune recognition of tumor cells Dr.T.V.Rao MD 18
  19. 19. • The Programme Created by Dr.T.V.Rao MD for Medical Students in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 19

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