Tumor Immunology PDF

Cancer Immune surveillance Immune evasion Cancer immunotherapy Introductio n Cell growth & cell death are normally balanced so that a stable number of cells are maintained in a given tissue. Occasionally, however, cells arise that no longer respond to the usual checks and...

Cancer Immune surveillance Immune evasion Cancer immunotherapy Introductio n Cell growth & cell death are normally balanced so that a stable number of cells are maintained in a given tissue. Occasionally, however, cells arise that no longer respond to the usual checks and balances for division and death. These are tumor cells. Canc er How does cancer arise? Dysregulated cell growth & proliferation => Transformation A clone of cells expanding indefinitely => A tumor Tumor cells => the body and cause diseases => Cancer  What causes dysregulated cell growth & proliferation? Intrinsic factors - Genetic mutations on Oncogenes & Tumor suppressor genes Environmental factors – Radiation, Carcinogens Microbial infections – Viruses (viral oncogenes) Bacteria  Key Concepts in Tumor immunity 1.Tumors express Ags that are recognized as foreign by the host immune system. 2. Immune responses frequently fail to prevent the growth of tumors. 3. The immune system can be activated by external stimuli to effectively kill tumor cells and eradicate tumors.  Tumor Antigens 1. Tumor-Specific Transplantation Antigens (TSTAs): Antigen that are expressed on tumor cells but not on normal cells were called tumor-specific.  Tumor Antigens 2. Tumor-Associated Transplantation Antigens (TATAs): Tumor antigens that are also expressed on normal cells were called tumor- associated antigens; in most cases, these antigens are normal cellular constituents whose expression is aberrant or dysregulated in tumors. Immune Surveillance A. Innate: 1. NK cells: NK cells kill many types of tumor cells, especially cells that have reduces class I MHC expression and can escape killing CTLs.  Immune Surveillance A. Innate: 2. Cytokines: Cytokines with antitumor activity are secreted by macrophages. - TNF: TNF-α and TNF-β can stimulate necrosis of the tumor cell. TNF-α also inhibit angiogenesis, the growth of new blood vessels by decreasing blood fl ow to the tumor.  Immune Surveillance - Interferons: Are another group of cytokines with anti tumor activity. IFN-α , IFN-β and IFN-γ have all been shown to increase MHC I expression on tumor cell surface. IFN-γ may also inhibit proliferation of tumor cells.  Immune Surveillance B. Adaptive: - antibodies: are known to be generated against certain tumor-specific antigens present on the surface of malignant cell. - CTL: direct killing! - DTH: activating macrophages, which attack and kill tumor cell.  Immune Evasion A. Antibody enhancement of tumor growth: The antitumor antibodies may bind to the antigens on the tumor cells, masking the antigens and blocking the ability of CTL cells to bind and kill the tumor cell. Antibody bound to tumor antigen may inhibit binding of Fc receptors on macrophages, dendritic cells, and NK cells.  Immune Evasion B. Antibody modulation of tumor antigen: The antigens disappear for a time and then reappear when the antibody is eliminated. Cells that do not express the antigen are no longer target of other adaptive immune responses. C. Modulation of MHC I expression: Class I MHC expression may be down- regulated on tumor cells so that they cannot be recognized by CTLs.  Cancer Immunotherapy A. Cytokine therapy. B. Monoclon al Antibodie s. A. Cancer vaccines.  Cancer Immunotherapy B. Monoclonal antibodies: 3 E of tumor immunology Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion, SCIENCE 25 Mar 2011  Summary Cancer cells have unregulated rates of cell growth and invade healthy tissue. Genetic mutations, radiation, Viruses and Bacteria are the causes of dysregulated cell growth & proliferation. Innate immune responses against tumors include NK cell killing of tumor and macrophage production of antitumor cytokines. Adaptive immune response against  Summary Immune evasion by tumor cells facilitate survival of malignant cells. Cancer immunotherapy is designed to increase the immune response against cancer cells, Cytokines and monoclonal antibodies have proven to have some limited effects in treating certain cancers. Vaccination, either to prevent development of a type of cancer or to inhibit recurrence of a tumor within a patient, continues to be explored. Referen ce Lippincott’s illustrated reviews , Immunology; Thao Doan MD, Roger Melvold PhD , Susan Viselli PhD, Carl Waltenbaugh PhD.