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Immunology in Head and Neck Cancer

Immunology in Head and Neck Cancer. Stephanie Cordes, MD Christopher Rassekh, MD February 11, 1998. Tumor Immunology. recognize and react against tumors prevent initial appearance or limit growth recognition not as effective histology shows mononuclear infiltrate

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Immunology in Head and Neck Cancer

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  1. Immunology in Head and Neck Cancer Stephanie Cordes, MD Christopher Rassekh, MD February 11, 1998

  2. Tumor Immunology • recognize and react against tumors • prevent initial appearance or limit growth • recognition not as effective • histology shows mononuclear infiltrate • patients with impaired immunocompetence • complex role

  3. Malignant Transformation • result of errors in genetic programming • chemical, physical, or viral carcinogens • multistep process • initiation : alterations in cellular DNA • promotion : altered presentation of genetic information • progression : abnormal phenotypes cloned

  4. Risk Factors for Head and Neck Cancer • Tobacco : carcinogens initiate and promote • Alcohol : additional promoter • Viruses : Ebstein-Barr and HSV • Nutritional status • Ionizing radiation : injures cellular DNA • Interference with immunity

  5. Immunosuppression • etiology is multifactorial • alcoholism: abnormalities in B and T cells • malnutrition: impairs B and T cell response • viruses: effect immunity • aging: cellular immunity wanes • tobacco: decrease cytotoxicity and reactivity

  6. Immune Recognition of Tumors • immunosurveillance • tumor-specific antigens • tumor-associated antigens • monoclonal antibody technology • major histocompatibility complex • still inadequate immune response to tumor

  7. Immunologic Escape • tumor kinetics • antigenic modulation • antigen masking • blocking factors • tolerance • genetic factors • tumor products • growth factors

  8. Immune Response to Tumor • Cellular immune system • Humoral immune system

  9. Cell-mediated Immunity • helper, suppressor, and cytotoxic lymphocytes • activation produces lymphokines • patients have altered immune function • peripheral total lymphocytes • Wanebo et al -decrease in total B and T cells and decreased stimulation

  10. Regional Immune Reactivity • draining lymph node morphology • Berlinger et al - evaluated 84 patients • active immunological response - greater five year survival • depleted or unstimulated response - no patients alive at five years • relationship between regional immunoreactivity and survival

  11. Humoral Immunity • augments cellular response • immunoglobulins • serum glycoproteins produced by B cells • specificity in binding to substrate • two heavy and two light chains • heavy chain type determines class • variable region is antigen binding site

  12. Response to Cancer • immunoglobulins : IgG and IgA primarily • IgG : functions by fixing complement and via ADCC • IgA : confers protective effect to tumor • immune complexes : elevated in patients • cytokines : interleukin, interferon, growth factor, and colony-stimulating factor

  13. Interferon • three subclasses • type I : interferon alpha and beta • type II : interferon gamma • mediate a large range of biologic responses • interferon gamma • direct cytotoxic effects • combined with chemotherapy • enhances antitumor effects of other cytokines

  14. Interleukins • Interleukin 1 • immunologic, inflammatory, and reparative • induces production of interleukin 2 • Interleukin 2 • produced by activated T lymphocytes • stimulates T, B, and NK cell proliferation • Interleukin 4 • Tumor growth factor beta

  15. Potential for Therapy • Active immunotherapy • administer agents that activate immune reaction • goal is to stimulate areas responsible for antitumor immunity • Passive immunotherapy • administer externally stimulated immunologic components • initially obtained from patient

  16. Active Immunotherapy • Tumor Vaccines : development limited • Biological Response Modifiers • BCG • interferon • interleukin 2

  17. Passive Immunotherapy • Monoclonal Antibodies • Cytotoxic Reagents • radioisotopes • toxins • chemotherapeutic drugs • cytokines

  18. Conclusion • immunosuppression more frequent • patients have leukocytes with antitumor reactivity • attempts at immunotherapy are not effective • study may lead to improvement in diagnosis and to determining prognosis

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