1. Evading Immune Responses and Tumor Immunology
Amy Lovett-Racke, PhD Associate Professor Department of Microbial Infection and Immunity

2. Cancer and Its Interactions with the Immune System
Peter Parham
The Immune System
Third Edition
Chapter 16
Cancer and Its Interactions with the Immune System
Copyright © Garland Science 2009

3. Learning Objectives
Know the difference in tumor-specific and tumor-associated antigens.
Understand the evidence that the immune system limits the development of cancer.
Compare and contrast the role of NK cells and CD8 T cells in the eradication of tumor cells.
Understand the mechanisms of immune evasion by cancer cells.

4. Benign versus Malignant Tumors
mutations – alterations in DNA
tumor (swelling) = neoplasm (new growth)
oncology – branch of medicine dealing with tumors
Encapsulated, localized and limited in size.
Can continue to grow by breaking through basal laminae and invading adjacent tissue.

5. Common Tissues of Cancer Origin in the USA
Carcinoma – cancers of epithelial cells; Sarcoma – cancers of other cell types.
Cancers of the Immune System
Leukemia – cancer of circulating immune cells
Lymphoma – solid lymphoid tumors
Myeloma – tumor of plasma cells in bone marrow

6. Multiple Mutations are Required for Cancer Development
Malignant transformation – when a cell has mutated such that it has become cancerous.
Proto-oncogens – genes that normally contribute positively to the initiation and execution of cell division.
Oncogenes – mutant forms of proto-oncogenes that contribute to malignant transformation.
Tumor suppressor genes – encode proteins that prevent the unwanted proliferation of mutant cells.

7. Some Cancers are Associated with Viruses
Mutagen – chemical or physical agent that damage DNA in such a way as to cause an increased rate of mutations.
Carcinogen – mutagens that are known to increase the risk of cancer.
Oncogenic virus – viruses that have the potential to transform cells and promote tumor formation.

8. Common Characteristics of Cancer Cells
Immunosurveillence or Cancer Immunosurveillence – the ability of the immune system to detect and eliminate tumors at an early stage.

9. Rate of Growth of Cancer

10. MHC is Critical in Immune Recognition of Tumors
Alloantigens – antigen that differs between members of the same species, such as HLA molecules. Alloantigens are recognized as foreign and elicit adaptive immune responses to eradicate the antigen.

11. Tumor-Specific Antigens
Tumor-specific antigen – antigen expressed on tumor cells but not on normal cells.
Tumor-associated antigen – antigen expressed on tumor cells but also found on normal cells, often in smaller amounts.

12. Antigens Commonly Mutated in Cancer

13. Generation of Novel Tumor Antigens

14. Evasion of the Immune Response by Tumors
NK cell gd T cell
MIC
NKG2D

15. Evasion of the Immune Response by Tumors
CD8
cancer cell
CD8 T cell
tumor antigen
Cancer Cell

16. Evasion of the Immune Response by Tumors
Tumor antigen
Tumor antigen
If a tumor antigen is presented by an activated macrophage or mature dendritic cell, B7 (CD80/86) will be present on the antigen presenting cells (APCs) and the tumor-specific CD8 T cell will be able to become activated and kill tumor cells.
However, APCs are often not activated by tumors and therefore, the APCs remain in an immature or inactivated state. These APCs will not express the costimulator molecule B7 (CD80/86) and therefore, T cells specific for the tumor antigens will not become activated. They will become anergic or unresponsive, allowing the tumor to go undetected by CD8 T cells.

17. Evasion of the Immune Response by Tumors

18. Vaccination with Tumor Antigens

19. Monoclonal Antibodies Detect and Treat Cancer
monoclonal antibody – antibodies produced by a single B cell clone and thus are all identical in structure and antigen specificity.

20. Monoclonal Antibodies Detect and Treat Cancer

21. Monoclonal Antibodies Detect and Treat Cancer

22. Monoclonal Antibodies Detect and Treat Cancer

23. Monoclonal Antibodies Detect and Treat Cancer

24. Things You Should Know
Difference between tumor-specific and tumor associated antigens.
Evidence that the immune response limits the development of cancers.
Primary immune mechanisms to recognize and kill tumor cells
CD8 T cells
NK cells
Mechanisms of immune evasions by cancers.
Cleavage of Mic proteins on tumor cells and internationalization of NKG2D by NK cells and γδ T cells.
Down regulation of MHC class I to evade CD8 T cells.
Down regulation of tumor antigens so they are undetectable by CD8 T cells.
Lack of costimulatory molecules on antigen presenting cells, resulting in anergic T cells.
Recruitment of Tregs to the tumor environment, and production of cytokines (TGFβ and IL-10) to suppress antigen-specific T cells in the tumor environment.

25. Evading Immune Responses Quiz

26. Thank you for completing this module
Questions?