Chapter 19 Cancer and the Immune System Dr. Capers

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