Cancer and the Immune System

1. Cancer and the Immune System Prepared by: Keerstin Throm Kevin Strozyk

2. Overview of Topics Origin and Terminology Oncogenes and Cancer Induction Tumor Antigens Tumor Evasion of the Immune System Immunotherapy

3. 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.

4. Tumor Growth and Metastasis

5. 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.

7. Conversion of Proto-Oncogenes to Oncogenes Three major mechanisms • Carginogens • Viruses • Radiation

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

9. Progression of Metastatic Colon Cancer • A multistep process which occurs with a series • of morphologic stages.

10. Gene Translocation

11. 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

13. Tumor Specific Transplantation Antigens

15. 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

16. 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

17. 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-α, -β, -γ and TNF-α, -β 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.