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Chapter 19 Cancer and the Immune System Dr. Capers. Immunology. Cancer. Altered self cells Unregulated mitosis Produces tumor (neoplasm) Benign – does not invade healthy tissue Malignant – grows and becomes invasive Exhibit metastasis.
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Chapter 19 Cancer and the Immune System Dr. Capers Immunology
Cancer • Altered self cells • Unregulated mitosis • Produces tumor (neoplasm) • Benign – does not invade healthy tissue • Malignant – grows and becomes invasive • Exhibit metastasis
Malignant cancers are classified according to embryonic origin of tissue • Carcinomas • Endodermal or ectodermal • Skin or epithelial lining of internal organs and glands • Colon, breast, prostate, lung • Leukemias and lymphomas • Tumors of hematopoietic cells of bone marrow • Leukemias proliferate as single cells • Lymphomas grow as tumor masses • Sarcomas • Mesodermal connective tissue • Bone, fat, cartilage
Malignant transformation • Ability for cell to form cancer • Decreased requirements for growth factors • No longer anchorage dependent • What can cause this? • Various chemical agents • Radiation • viruses
Genes that code for proteins involved in cell proliferation are called proto-oncogenes; mutations in these genes can lead to increased proliferation
Chromosomal translocations • Can lead to movement of proto-oncogenes • This can lead to increased transcription and translation of the protein
Induction of cancer is a multi-step process • Multiple and subsequent mutations
Tumors of Immune System • Leukemias or Lymphomas • Lymphomas • Solid tumors in lymphoid tissue • Include Hodgkin’s and non-Hodgkin’s lymphomas • Leukemias • Proliferate as single cells • Lymphoid or myeloid lineage • Acute – appear and progress rapidly, tend to rise in immature cells • Chronic – less aggressive and slow, tend to rise in mature cells, tend to be in adults
Tumor Antigens • Tumor-specific transplantation antigens (TSTAs) • Unique to tumor cells • May arise due to mutation • Are presented on Class I MHC • Tumor-associated transplantation antigens (TATAs) • Proteins expressed on normal cells • Inappropriate expression of embryonic gene • Overexpression of normal protein • Some antigens are tumor specific
Oncofetal antigens • Found on normal fetal cells • Only meant to be expressed during embryological development • Suppressed after development of fetus is completed • If expressed later in adult, could induce immune response • Immune system may see these as nonself • Can lead to cancer • ~90% of colorectal cancer have CEA (carcinoembryonic antigen)
Tumor Invasion of Immune System • Anti-tumor antibodies • Might actually block sites for CTL to bind • Tumor cells might express less Class I MHC • This prevents CTL-mediated death • Tumor cells may provide poor costimulatory signals
Cancer Immunotherapy • Manipulation of costimulatory signals • Enhancement of antigen-presenting cells • Cytokine therapy • Interferons • Tumor necrosis factors • Monoclonal Abs may be used for some tumors • Immunotoxins may be linked to kill specific tumor cell, still being researched • Radioactive isotope, drugs