3Learning ObjectivesKnow 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.
4Benign versus Malignant Tumors mutations – alterations in DNAtumor (swelling) = neoplasm (new growth)oncology – branch of medicine dealing with tumorsEncapsulated, localized and limited in size.Can continue to grow by breaking through basal laminae and invading adjacent tissue.
5Common Tissues of Cancer Origin in the USA Carcinoma – cancers of epithelial cells; Sarcoma – cancers of other cell types.Cancers of the Immune SystemLeukemia – cancer of circulating immune cellsLymphoma – solid lymphoid tumorsMyeloma – tumor of plasma cells in bone marrow
6Multiple 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.
7Some 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.
8Common Characteristics of Cancer Cells Immunosurveillence or Cancer Immunosurveillence – the ability of the immune system to detect and eliminate tumors at an early stage.
10MHC 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.
11Tumor-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.
14Evasion of the Immune Response by Tumors NK cell gd T cellMICNKG2D
15Evasion of the Immune Response by Tumors CD8cancer cellCD8 T celltumor antigenCancer Cell
16Evasion of the Immune Response by Tumors Tumor antigenTumor antigenIf 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.
24Things You Should KnowDifference 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 cellsCD8 T cellsNK cellsMechanisms 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.