Host Defense Against Tumors (Tumor Immunity)

.immune surveillance -implies that a normal function of the immune system is to survey the body for emerging malignant cells & destroy them, it is imperfect .strongest argument for its existence is increased frequency of cancers in immuno-deficient hosts .but most cancers occur in persons who do not suffer from any overt immuno-deficiency

.cancer immunoediting -includes immune surveillance plus “sculpting” the immunogenic properties of tumors to select tumor cells that escape immune elimination CTLs are the major immune defense mechanism against tumors, recognize peptides derived from cytoplasmic proteins that are bound to class I major histocompatibility complex (MHC) molecules

Tumor Antigens .classification based on molecular structure & source -products of mutated proto-oncogenes, tumor suppressor genes, & other mutated genes are not major targets of CTLs in most patients

-products of over expressed or abnormally expressed normal cellular proteins .tyrosinase in melanoma .cancer-testis antigens -tumor antigens produced by oncogenic viruses (HPV, EBV)

-onco-fetal antigens (CEA, AFP) -onco-fetal antigens (CEA, AFP) .proteins expressed at high levels on cancer cells & in normal developing fetal but not adult tissues .amounts are increased in tissues & circulation in inflammatory conditions .no evidence that the antigens are targets of antitumor immunity .used as markers in tumor diagnosis

-altered cell surface glycolipids & glycoproteins (gangliosides, blood group antigens, mucins) .markers for diagnosis .target for cancer therapy with specific antibodies

-cell type-specific differentiation antigens -cell type-specific differentiation antigens .are specific for particular lineages or differentiation stages of various cells .are normal self-antigens (do not induce immune response) in tumor-bearing hosts .are potential targets for immunotherapy & for identifying tissue of origin of tumors (CD20 in B cell lymphoma)

Antitumor Effector Mechanisms .natural killer cells (NKC) -first line of defense against tumors .cytotoxic T lymphocytes .macrophages NK cells, T cells & macrophages collaborate in antitumor reactivity .antibodies -no defensive role against cancer -therapeutic use of monoclonal antibodies in lymphoma (CD20)

Escape of Immune Mechanisms .through -selective overgrowth of antigen- negative variants -loss or reduced expression of MHC class 1 molecules -antigen masking -apoptosis of cytotoxic T cells

-lack of costimulation -lack of costimulation .sensitization of T cells requires two signals, one presented by MHC molecules & the other by co- stimulatory molecules .tumor cells often do not express costimulatory molecules -immunosuppression by .chemical carcinogens .ionizing radiation .tumors &/or their products

Promotion of Tumors Growth by the Immune System Promotion of Tumors Growth by the Immune System .through -activated lymphocytes & macrophages produce growth factors for tumor cells -regulatory T-cells & subtypes of macrophages may suppress host response to tumors -enzymes (MMPs), enhance tumor invasion