7. Cancer immunobiology

Question 1

What are tjhe 3 types of tumour antigens? Describe the differences between them.

Answer 1

1. Tumour-specific antigens (TSAs)
2. Tumour-associated antigens (TAAs)
3. Oncofoetal antigens

TSAs can be easily distinguished from normal antigens as they are only present on tumour cells.

TAAs are recognised as they are expressed at high levels on tumour cells and low levels in normal cells.

Oncofoetal antigens are inappropriately expressed on tumour cells as they should only be expressed during foetal development.

Question 2

Describe tumour editing.

Answer 2

Tumour immune editing is a more comprehensive model that describes how immune-resistance can develop in tumours. It can be divided into 3 phases:

1. Elimination (Immune surveillance)
2. Equilibrium
3. Escape

Elimination occurs when the immune system identifies and eliminates tumour cells using immune surveillance.

Equilibrium occurs if some cancer cells were not eradicated in the elimination phase. This is a transitory phase where the immune system and developing tumour are in a balanced state that can last for several years. The tumour cells can remain dormant, or continue acquiring genome modifications that can alter tumour-specific antigens, making them unrecognisable by the immune system.

Escape occurs when the immune system is unable to restrict tumour growth, and the cancer cells can begin to grow and expand uncontrollably. This can occur if:

· Tumour cells may fail to produce tumour antigens

· Tumour cells might have mutations in MHC so cannot process antigens

· Tumour cells might produce immunosuppressive cytokines

Question 3

How are immune checkpoints evaded by cancer cells? Give an example of one.

Answer 3

An example of this is the PD-1 receptor found on T cells that requires the PD-L1 protein on healthy cells to inhibit the T cell killing the cell. This allows tumour cells with PD-L1 to escape the immune response. Anti-tumour strategies include blocking immune checkpoints – including using Anti-PD-1 and anti-PD-L1 antibodies to increase tumour cell death.

Question 4

What are immune checkpoints?

Answer 4

Immune checkpoints generally function to prevent autoimmunity.

Question 5

Describe the theory of immune surveillance.

Answer 5

Immune surveillance is the theory that the immune system protects the body against cancer as well as infectious agents.

The Immune surveillance theory assumes that there is only a qualitative difference between tumour antigens and normal antigens – ignoring quantitative differences. It also assumes that cancers only develop when the immune system is impaired, or if cancer cells lose their immunogenicity.

The principal mediators of immune surveillance are:

· Professional Antigen Presenting Cells

o Dendritic cells, macrophages and B cells internalise antigens by phagocytosis and present the peptide fragments on their MHC II complex

o This is recognised by the TCR and the co-stimulatory signal is given by CD28, CD80 and CD86.

· T cells

o Helper T cells and Cytotoxic T cells

o Cytotoxic T cells are activated when they recognise the MHC I and expand (memory and activated cytotoxic) and destroy target cells.

Question 6

What are the evidence supporting and refuting immune surveillance theory?

Answer 6

This is supported by immunosuppressed patients (medication or HIV infected) as well as young and old patients showing higher occurrence of tumours. However, evidence against this theory includes ‘nude mice’ not developing cancers and immunosuppressed patients exhibiting increased risk of certain cancer, but not other common cancers such as lung, breast and colon cancer.

Question 7

How do oncoviruses cause cancer?

Answer 7

· Chronic inflammation – causes rapid increased cell division, which increases the likelihood of genetic mutations arising.

· Damage DNA directly

· Alter immune system preventing it from fighting off immune cells