Immune response to cancer

Question 1

What are neo-antigens?

Answer 1

Antigens which arise from somatic mutations which produce abnormal peptide proteins which are then expressed by MHC complexes on cells

Question 2

What are viral antigens caused by?

Answer 2

Oncogenic viruses

Question 3

What type of mutations are responsible for tumour antigens?

Answer 3

Driver mutations

Question 4

How to tumours become resistant to CD8+ T cells?

Answer 4

By downregulating MHC class molecules or molecules involved in antigen processing in proteosome.

Question 5

How do tumours inhibit T-cell activity?

Answer 5

through CTLA-4 and PD-1

Question 6

Name some cells in which tumours can promote to activate a immuno-suppressive environment

Answer 6

T regs, Myeloid derived suppressor cells, tumour associated macrophages

Question 7

How does CTLA-4 inhibit T cell activity?

Answer 7

By raising the stimulatory threshold or by inhibiting proliferation

Question 8

CTLA-4 acts as an alternative receptor for which co-stimulatory signal?

Answer 8

B7

Question 9

Why are anti-CTLA-4 antibodies used?

Answer 9

to inhibit T regulatory cells (they are expressed on t regs)

Question 10

What does PD-L1 regulate?

Answer 10

Regulates the induction and maintenance of the peripheral tolerance and protects tissue from autoimmune attack

Question 11

What does the interaction between PD-1 and PD-L1 regulate?

Answer 11

Inhibits the activity of effector CD8 T cells by suppression of cytokine production and cytotoxicity

Question 12

How are MDSCs immunosuppressive functions mediated.

Answer 12

Expression of suppressive factors
Reducing T-cell L-selectin expression and Treg induction
Disruption of T-cell metabolism, activation, proliferation and in turn their tumour-cell killing capacity

Question 13

Explain adenosines function in immunosuppression.

Answer 13

T regs express the ecto-enzymes CD39 and CD73 on their cell surface, which convert ATP to AMP and AMP to adenosine. Adenosine binds to the adenosine A2A receptor on the effector T cells and suppresses their anti-tumour function by activating cyclic AMP (cAMP)-PKA signalling cascade. Extracellular ATP which is an essential as a substrate for CD39, is presumed to be derived from apoptosis of cells in the tumour micro-environment.

Question 14

Where do monoclonal antibodies target which treat B cell tumours.

Answer 14

CD20 (Anti-CD20 monoclonal antibodies)

Question 15

What are examples of monoclonal antibodies used to treat cancer?

Answer 15

Herceptin, avastin (VEGF)

Question 16

What is adoptive T cell therapy often combined with?

Answer 16

Combined with administration of T cell stimulating cytokines such as interleukin-2 (IL-2) and traditional chemotherapy

Question 17

Describe the CAR structure which are currently in use.

Answer 17

CARs currently in use have a single chain antibody-like extracellular portion with both heavy-and light-chain variable domains.

Question 18

Give an example of a adverse effect of CAR T cells.

Answer 18

Cytokine release syndrome (CRS)

Question 19

Give an example of an immune checkpoint inhibitor.

Answer 19

Pembrolizumab (Keytruda)

Question 20

Which receptor does pembrolizumab bind?

Answer 20

PD-1 receptor

Question 21

Which HPV types are responsible for almost 70% of cervical cancers.

Answer 21

HPV type 16 and 18

Question 22

Which HPV types does cervarix block?

Answer 22

HPV types 16 and 18