Tumour Immunology Flashcards
Describe an experiment to demonstrate the immunogenicity of tumours.
- A mouse injected with a carcinogen will develop a tumour.
- If cells from this tumour are transplanted into another mouse, this mouse will develop the same tumour as expected.
- However if cells from a mouse with the tumour are taken and irradiated (so that the tumour cell can no longer replicate), and then transplanted into another mouse, that mouse will develop resistance to developing that cancer if it is challenged with a tumour cell.
Another way of demonstrating the same thing:
- If a tumour is surgically removed from a mouse such that it is completely free of the tumour, and it is then later treated with cells from the removed tumour, it will not develop the tumour again.
In mice models, which cells were required for the tumour to induce an immune response?
T cells.
What is cancer immunosurveillance?
The concept that the immune system can recognise precursors of cancer and, in most cases, destroy these precursors before they become clinically apparent.
What is cancer immunoediting?
- The concept that the immune system edits the immunogenicity of tumours by a process of natural selection that may eventually result in the formation of a tumour. It consists of the 3 Es:
1 - Elimination - immune-mediated destruction of most cancer cells.
2 - Equilibrium - a dynamic equilibrium between the immune system and any tumour cell that has survived the elimination phase. The immune response is enough to contain, but not eliminate, these cells.
3 - Escape - the tumour cell variants selected in equilibrium now grow out in an immunologically intact environment.
List the signals required for a T cell to become activated.
1 - A first signal is recognised through the T cell receptor in the form of a protein presented on MHC on an antigen-presenting cell.
2 - A second costimulatory signal is required that can be delivered by a number of molecules on the surface of a T cell interacting with molecules on the surface of an antigen-presenting cell.
Give an example of an interaction between molecules on the surface of a T cell and molecules on the surface of an antigen-presenting cell to produce a costimulatory signal.
CD80 and CD86 on the surface of antigen presenting cells often interacts with CD28 on the surface of T cells.
Describe the process of generating an immune response to a tumour.
1 - Tissue damage at the site of a tumour results in tumour antigen release.
2 - A dendritic cell presents this tumour antigen.
3 - The dendritic cell travels to a lymph node and presents the antigen to many T cells.
4 - The T cells whose T cell receptors recognise the tumour antigen on the dendritic cell undergo clonal expansion.
5 - The selected T cells leave the node and enter the circulation to travel to the site of the tumour, where they elicit an immune response.
List 5 mechanisms that explain why tumours originating in the body are not protected by tolerance to self antigens.
1 - Some proteins might become mutated during the formation of the cancer, such that they are no longer recognised as self antigens.
2 - Some normal self antigens might be overexpressed, resulting in an immune response to those antigens.
3 - Lineage-specific antigens might be inappropriately expressed in the tumour. Although these are self, an immune response is generated at the expense of damage to that lineage.
4 - Abnormal post-translational modification of self proteins in the tumour.
5 - The tumour carries a viral protein.
List 3 examples of normal self antigens that can be overexpressed in tumours, resulting in an immune response.
1 - Oncofoetal antigens which are normally expressed in embryogenesis, such as CEO and AFP.
2 - Cancer-testis antigens (MAGE) in melanomas.
3 - Telomerase.
List 4 lineage-specific antigens that can be inappropriately expressed in tumours to cause an immune response.
In which cancers are these antigens overexpressed?
In melanomas:
1 - Mart1 / Melan A complex.
2 - Gp100.
3 - Tyrosinase.
In B cell lymphomas:
4 - Surface immunoglobulins.
Give an example of an antigen that can be abnormally modified post-translationally to cause an immune response.
In which cancers is expression of this antigen implicated?
- Underglycosylated mucin.
1 - Breast cancer.
2 - Pancreatic cancer.
List 2 oncogenic viruses.
Which tumours do they cause?
1 - HPV.
- Cervical cancer.
2 - EBV.
- Hodgkin’s lymphoma.
- Nasopharyngeal carcinoma.
How can an immune response destroy a tumour without targeting the tumour cells directly?
By targeting the tumour stroma, e.g. by identifying endothelial markers.
List 4 characteristics of a good target antigen for tumour immunotherapy.
1 - The antigen is tumour-specific (reduces toxicity of the immune response).
2 - The antigen is shared amongst other tumour types (the treatment is widely applicable).
3 - The antigen is critical for tumour growth / survival (to ensure there is a lack of antigen-loss tumour cell variants).
4 - There is a lack of immunological tolerance to the tumour tissue (to ensure that there maximally high avidity T cells are produced).
List 3 good examples of tumour antigens that are highly tumour-specific.
1 - Mutated self-proteins.
2 - Viral antigens.
3 - Cancer-testis antigens.