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TUMOR IMMUNOLOGY

TUMOR IMMUNOLOGY. Tumor Immunology. Does it exist? i.e., does the immune system recognize and eradicate cancer cells? Is there any evidence for immunological surveillance (Burnett and Thomas)? How can the immune system recognize cancer if it is essentially self-tissue? (Tolerance)

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TUMOR IMMUNOLOGY

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  1. TUMOR IMMUNOLOGY

  2. Tumor Immunology • Does it exist? • i.e., does the immune system recognize and eradicate cancer cells? Is there any evidence for immunological surveillance (Burnett and Thomas)? • How can the immune system recognize cancer if it is essentially self-tissue? (Tolerance) • If it does not- can it be made to do so? Immunization designed to Break Tolerance

  3. The immune system can destroy self-tissue quite effectively in autoimmunity, and in a tissue-specific (antigen-specific) manner: (thyroiditis, hepatitis, pancreatitis (diabetes), vitiligo, ITP, AIHA, gradt rejection etc.). • So, self-tissue destruction can be potent.

  4. Immunization with Tumor Cells CanInduce Protective Immune Response

  5. Tumor Antigens Are Unique to Individual Tumors • Candidate Tumor Antigens..many more to come through genomics • Shared Tumor Antigens (common across tumors and tumor types) Allows single therapy to be applicable for many patients 1. Cancer/testes genes 2. Differentiation associated antigens 3. Others including gangliosides, MUC- 1, etc.,

  6. Unique Tumor Antigens (requires tumor specific therapy) Antigenic modulation would potentially interfere with malignant phenotype. 1. Overexpressedproto-oncogenes EGFR, HER2 2. Point mutations: ras, catenin, CDC27, CDK4, Bcr/Abl 3. Viral Antigens: Human papilloma virus, EBV, Hepatitis B

  7. Tumor markers • Produced either by the tumor itself or by the body in response to the presence of cancer. • The utility in clinical medicine is to support the diagnosis, determining in the response to therapy, follow up , and prognosis

  8. Tumor markers Method Immunohistochemistry • Categorization of undifferentiated malignant tumors - keratin for carcinoma ( epithelial origin) - desmin for neoplasm of muscle cell origin • Categorization of leukemia and lymphoma • Determination of site of origin of metastatic cancer

  9. Detection of molecules that have prognostic or therapeutic significance - breast cancer : ER, PR, c-erbB2, p53 BRCA1/ BRCA2 - ovarian cancer / endometrial cancer : ER, PR, c-erbB2, BRCA1/ BRCA2

  10. Summary • Tumor Immunology: 1) Immunological recognition of tumor occurs. 2) Tumors emerge in individuals having overcome 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

  11. Summary • 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.

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