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