Tumour immunology

Question 1

List 3 key concepts in tumour immunology.

Answer 1

1. Tumours express Ags - foreign to ISys.
2. ISys. frequently fail to prevent growth of tumours
3. ISys. can be activated by ext. stimuli to effectively kill tumour cells

Question 2

Describe the three phases related to the tumour growth and the immune system.

Answer 2

• Elimination: Innate & adaptive immunity remove transformed cells (hi immunogenic)
• Equilibrium: Hi immunogenic eliminated by ISys. but some poor immunogenic not detected & survive
• Escape: proliferation of immunogenic transformed cells

Question 3

What is cancer immunoediting and in what phase does it occur?

Answer 3

a) process that eliminates highly immunogenic cancer cells

b) Elimination phase?

Question 4

Which lymphocyte subsets are involved in direct killing of tumour cells and describe the mechanisms by which they destroy the target tumour cell.

Answer 4

• NK cells: respond to absence/reduced of MHC I expression; to ligands expressed by tumour cells; OR IgG-coated tumour
• CD8 Tcytotox. cells: kill cells via CD8 receptor OR expression of tumour Ag via MHC I

Question 5

How do tumour antigens come about? List two types of tumour antigen

Answer 5

a) mutation in DNA => production of tumour Ag
b) types:
- Tumor-specific mutated oncogene or tumour suppressor
- Germ cell

Question 6

How do cancers evade immune surveillance?

Answer 6

• become weakly immunogenic
• stimulate inhibitory mechanisms => suppress ISys.
• secretion of tumour product suppress IResp.
• Regulatory T cells may suppress T cell activity (keep them off)
• tumour associated macrophage may suppress T cell resp.
  => promote tumour growth & proliferation

Question 7

Macrophages can inhibit or promote tumour growth. Which phenotypes are involved and how do they affect the tumour?

Answer 7

• Inhibit: M1 > kill tumour cells by recognising DAMP from TLR of macro./WBC & activation by IFN-gamma from tumour-specific T cells
• Promote: M2 > enhance tumour growth by secrete mediators, that impair T cell activation & effector func., &

Question 8

Why do cancers with high mutation loads more likely to elicit an immune response?

Answer 8

bc mutations = different protein = distinct form non-self Ag = recognised as non-self & IR stimulated

Question 9

List and describe two immunotherapies currently being tested.

Answer 9

1. Adoptive cell therapy: Chimeric Ag Receptor T cell (CAR-T) therapy: use patient’s own T cell to kill cancer
2. T cell inhibitor blockade: tumour cells have inhibitory receptors (PD-1) so have anti-PD-1 Ab to bind to receptor => allow effective T cell response

Question 10

Explain adoptive therapy in relation to treatment of cancer.

Answer 10

• isolate patient’s lymphocytes (from blood or tumour) and culture in IL-2 & infused back in patient
• Lymphocytes may be transfected w/ CAR genes
  = better T cell activation = kill cancer cells