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PPT

  1. 1. Immunology in Head and Neck Cancer Stephanie Cordes, MD Christopher Rassekh, MD February 11, 1998
  2. 2. Tumor Immunology <ul><li>recognize and react against tumors </li></ul><ul><li>prevent initial appearance or limit growth </li></ul><ul><li>recognition not as effective </li></ul><ul><li>histology shows mononuclear infiltrate </li></ul><ul><li>patients with impaired immunocompetence </li></ul><ul><li>complex role </li></ul>
  3. 3. Malignant Transformation <ul><li>result of errors in genetic programming </li></ul><ul><li>chemical, physical, or viral carcinogens </li></ul><ul><li>multistep process </li></ul><ul><ul><li>initiation : alterations in cellular DNA </li></ul></ul><ul><ul><li>promotion : altered presentation of genetic information </li></ul></ul><ul><ul><li>progression : abnormal phenotypes cloned </li></ul></ul>
  4. 4. Risk Factors for Head and Neck Cancer <ul><li>Tobacco : carcinogens initiate and promote </li></ul><ul><li>Alcohol : additional promoter </li></ul><ul><li>Viruses : Ebstein-Barr and HSV </li></ul><ul><li>Nutritional status </li></ul><ul><li>Ionizing radiation : injures cellular DNA </li></ul><ul><li>Interference with immunity </li></ul>
  5. 5. Immunosuppression <ul><li>etiology is multifactorial </li></ul><ul><li>alcoholism: abnormalities in B and T cells </li></ul><ul><li>malnutrition: impairs B and T cell response </li></ul><ul><li>viruses: effect immunity </li></ul><ul><li>aging: cellular immunity wanes </li></ul><ul><li>tobacco: decrease cytotoxicity and reactivity </li></ul>
  6. 6. Immune Recognition of Tumors <ul><li>immunosurveillance </li></ul><ul><li>tumor-specific antigens </li></ul><ul><li>tumor-associated antigens </li></ul><ul><li>monoclonal antibody technology </li></ul><ul><li>major histocompatibility complex </li></ul><ul><li>still inadequate immune response to tumor </li></ul>
  7. 7. Immunologic Escape <ul><li>tumor kinetics </li></ul><ul><li>antigenic modulation </li></ul><ul><li>antigen masking </li></ul><ul><li>blocking factors </li></ul><ul><li>tolerance </li></ul><ul><li>genetic factors </li></ul><ul><li>tumor products </li></ul><ul><li>growth factors </li></ul>
  8. 8. Immune Response to Tumor <ul><li>Cellular immune system </li></ul><ul><li>Humoral immune system </li></ul>
  9. 9. Cell-mediated Immunity <ul><li>helper, suppressor, and cytotoxic lymphocytes </li></ul><ul><li>activation produces lymphokines </li></ul><ul><li>patients have altered immune function </li></ul><ul><li>peripheral total lymphocytes </li></ul><ul><li>Wanebo et al -decrease in total B and T cells and decreased stimulation </li></ul>
  10. 10. Regional Immune Reactivity <ul><li>draining lymph node morphology </li></ul><ul><li>Berlinger et al - evaluated 84 patients </li></ul><ul><li>active immunological response - greater five year survival </li></ul><ul><li>depleted or unstimulated response - no patients alive at five years </li></ul><ul><li>relationship between regional immunoreactivity and survival </li></ul>
  11. 11. Humoral Immunity <ul><li>augments cellular response </li></ul><ul><li>immunoglobulins </li></ul><ul><ul><li>serum glycoproteins produced by B cells </li></ul></ul><ul><ul><li>specificity in binding to substrate </li></ul></ul><ul><ul><li>two heavy and two light chains </li></ul></ul><ul><ul><li>heavy chain type determines class </li></ul></ul><ul><ul><li>variable region is antigen binding site </li></ul></ul>
  12. 12. Response to Cancer <ul><li>immunoglobulins : IgG and IgA primarily </li></ul><ul><li>IgG : functions by fixing complement and via ADCC </li></ul><ul><li>IgA : confers protective effect to tumor </li></ul><ul><li>immune complexes : elevated in patients </li></ul><ul><li>cytokines : interleukin, interferon, growth factor, and colony-stimulating factor </li></ul>
  13. 13. Interferon <ul><li>three subclasses </li></ul><ul><ul><li>type I : interferon alpha and beta </li></ul></ul><ul><ul><li>type II : interferon gamma </li></ul></ul><ul><li>mediate a large range of biologic responses </li></ul><ul><li>interferon gamma </li></ul><ul><ul><li>direct cytotoxic effects </li></ul></ul><ul><ul><li>combined with chemotherapy </li></ul></ul><ul><ul><li>enhances antitumor effects of other cytokines </li></ul></ul>
  14. 14. Interleukins <ul><li>Interleukin 1 </li></ul><ul><ul><li>immunologic, inflammatory, and reparative </li></ul></ul><ul><ul><li>induces production of interleukin 2 </li></ul></ul><ul><li>Interleukin 2 </li></ul><ul><ul><li>produced by activated T lymphocytes </li></ul></ul><ul><ul><li>stimulates T, B, and NK cell proliferation </li></ul></ul><ul><li>Interleukin 4 </li></ul><ul><li>Tumor growth factor beta </li></ul>
  15. 15. Potential for Therapy <ul><li>Active immunotherapy </li></ul><ul><ul><li>administer agents that activate immune reaction </li></ul></ul><ul><ul><li>goal is to stimulate areas responsible for antitumor immunity </li></ul></ul><ul><li>Passive immunotherapy </li></ul><ul><ul><li>administer externally stimulated immunologic components </li></ul></ul><ul><ul><li>initially obtained from patient </li></ul></ul>
  16. 16. Active Immunotherapy <ul><li>Tumor Vaccines : development limited </li></ul><ul><li>Biological Response Modifiers </li></ul><ul><ul><li>BCG </li></ul></ul><ul><ul><li>interferon </li></ul></ul><ul><ul><li>interleukin 2 </li></ul></ul>
  17. 17. Passive Immunotherapy <ul><li>Monoclonal Antibodies </li></ul><ul><li>Cytotoxic Reagents </li></ul><ul><ul><li>radioisotopes </li></ul></ul><ul><ul><li>toxins </li></ul></ul><ul><ul><li>chemotherapeutic drugs </li></ul></ul><ul><ul><li>cytokines </li></ul></ul>
  18. 18. Conclusion <ul><li>immunosuppression more frequent </li></ul><ul><li>patients have leukocytes with antitumor reactivity </li></ul><ul><li>attempts at immunotherapy are not effective </li></ul><ul><li>study may lead to improvement in diagnosis and to determining prognosis </li></ul>

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