Cancer and the Immune System

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Cancer and the Immune System

• Prepared by
• Keerstin Throm
• Kevin Strozyk

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Overview of Topics

• Origin and Terminology
• Oncogenes and Cancer Induction
• Tumor Antigens
• Tumor Evasion of the Immune System
• Immunotherapy

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Major Terminology

• Benign Tumor not capable of indefinite growth
• Malignant Invasive tumor that can grow
  indefinitely
• Metastasis Cancerous cells dislodged from tumor
  which are carried to other tissues where they
  proceed to proliferate.
• Carcinoma Tumor from Endodermal or Ectodermal
  tissue.
• Leukemia/Lymphoma Malignant tumors of the
  hematopoietic cells of the bone marrow.
• Sarcoma A tumor of the mesodermal connective
  tissues.

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Tumor Growth and Metastasis
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Oncogenes and Cancer Induction
Oncogenes vs. Proto-Oncogenes

• Oncogenes are the viral counterparts of cellular
  proto-oncogenes

• High degree of homology

• Both are derived from genes which encode various
  growth
• controlling proteins.

• Proto-oncogenes are capable of being converted
  to oncogenes
• by undergoing a mutation.

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Conversion of Proto-Oncogenes to Oncogenes
Three major mechanisms

• Carginogens

• Viruses

• Radiation

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• Translocation of a proto-oncogene from one
• chromosomal site to another, or to a separate
• chromosome, can cause a malignant transformation.

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Progression of Metastatic Colon Cancer

• A multistep process which occurs with a series
• of morphologic stages.

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Gene Translocation
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Tumor Antigens

• Tumor Specific Transplantation Antigens (TSTAs)
• Antigens are unique to tumor cells

• Chemically, physically, or virally induced.

• Tumor Associated Transplantation Antigens
  (TATAs)
• Antigens that are not unique to tumor cells

• Expression of an embryonic gene
• Overexpression of a normal cellular protein

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Tumor Specific Transplantation Antigens
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Tumor Associated Transplantation Antigens
Oncofetal Tumor Antigens

• Normally expressed early in fetal development

• When found on tumor cells, can be recognized as
  non-self

• Alpha-fetoprotein (AFP)
• Carcinoembryonic antigen (CEA)

Increased Expression of Normal Antigens

• Elevated expression of antigen present in a
  normal cell
• encoded by cellular oncogenes

• Neu protein expression in breast cancer cells

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Tumor Evasion of the Immune System
Antitumor Antibodies

• Act as a blocking factor by forming
• complexes with tumor antigens.

Antibodies Modulate Tumor Antigens

• Disappearance of tumor antigen on
• surface in response to specific antibodies

Low Levels of Class I MHC Molecules

• Has a profound effect on the cell-mediated
• cytotoxic T cell response.

Poor Costimulatory Signals

• Lack of costimulatory molecules cannot
• stimulate CTL response

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Cancer Immunotherapy
Manipulation of Costimulatory Signals

• Transfect genes for costimulatory signals (B7
  ligand) into tumor cells
• To activate CTLs.

Enhancement of APC Activity

• Transfect a gene for GM-CSF to increase
  macrophage activation

Cytokine Therapy

• Use of cytokines like IFN-a, -ß, -? and TNF-a,
  -ß which have direct
• antitumor activity.

Monoclonal Antibodies

• Can cause direct complement-mediated lysis, or
  can be conjugated
• with an agent which can be directly delivered
  to the tumor cell.

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