Chapter 19
Cancer and the Immune System
Dr. Capers
Cancer
Altered self cells Unregulated mitosis
○ Produces tumor (neoplasm)Benign – does not invade healthy tissueMalignant – grows and becomes invasive
- Exhibit metastasis
Malignant cancers are classified according to embryonic origin of tissue
○ CarcinomasEndodermal or ectodermalSkin or epithelial lining of internal organs and glandsColon, breast, prostate, lung
○ Leukemias and lymphomasTumors of hematopoietic cells of bone marrowLeukemias proliferate as single cellsLymphomas grow as tumor masses
○ SarcomasMesodermal connective tissueBone, fat, cartilage
Malignant transformationAbility 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 incell proliferation arecalled proto-oncogenes; mutations in thesegenes can lead to increasedproliferation
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 cellsInappropriate expression of embryonic geneOverexpression 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 researchedRadioactive isotope, drugs