The Immune System and Cancer

Question 1

What are the three primary role of the immune system in the prevention of cancer?

Answer 1

Eliminate or suppress viral infectious to protect from virus induced tumours
Eliminate pathogens quickly so that an inflammatory environment (conductive to tumorigenesis) does not occur
Identify and eliminate tumour cells

Question 2

What are the three stages of tumour immunoediting?

Answer 2

Elimination
Equilibrium
Escape

Question 3

When there is incomplete elimination of tumour cells by the immune system an equilibrium can establish between the immune system and developing tumour. T/F?

Answer 3

True

Question 4

What events occur within the tumour during the equilibrium period of immunoediting?

Answer 4

Tumour can continue to evolve, accumulating further changes that can modulate tumour-specific antigens and stress-antigens that they express in order to evade the immune system

Question 5

The immune system acts as a selective pressure on cancer cells. T/F?

Answer 5

True

Question 6

What happens in the escape phase of immunoediting?

Answer 6

Immune system is no longer able to contain tumour growth and a progressively growing tumour results

Question 7

What cell functions are regulated by the RAS/RAF/MAPK pathway?

Answer 7

cell cycle regulation
wound healing
tissue repair
integrin signalling
cell migration
expression of genes involved in the formation of new blood vessels

Question 8

How does the Ras/Raf/MAPK pathway become activated?

Answer 8

EGFR or PDGFR bind to a protein tyrosine kinase receptor

Question 9

After binding of EGFR to its receptor how does the Ras/Radf/MAPK pathway lead to activation of Ras?

Answer 9

EGFR becomes phosphorylated allowing docking of proteins such as GRB2 and SH2 to the activated receptor
This allows binding of SOS which promotes removal of GDP from Ras, which activates Ras

Question 10

After activation of Ras how does the Ras/Radf/MAPK pathway progress?

Answer 10

Ras activates Raf kinase
Raf kinase phosphorylates and activates MEK 1 which phosphorylates MEK2 which phoshoylates MAPK
Active MAPK can then activate a number of molecules to cause changes in gene expression

Question 11

What gene is responsible for making Raf protein?

Answer 11

BRAF gene

Question 12

How can mutations in BRAF gene lead to cancer?

Answer 12

This can cause the Raf protein to be continuously active allowing the transmission of message to the nucleus even in the absence of chemical signals
this allows uncontrolled growth and division of cells

Question 13

What is the most common mutation of the BRAF gene?

Answer 13

V600E mutation

Question 14

What is the mechanism of action of vemurafenib?

Answer 14

Interrupts RAF/MEK step on the Ras/Raf/MAPK pathway to prevent cell growth and division

Question 15

What type of cancer is vemurafenib most commonly used against?

Answer 15

Melanoma

Question 16

Describe the immunotherapy which is used against bladder cancer?

Answer 16

Bacillus clamette-guerin a weakened form of bacteria which causes tuberculosis, inserted into the bladder by a catheter and causes an immune response against the cancer cells

Question 17

Cytokine therapy can be used in the treatment of cancer. Describe how IFN alpha/beta affects cancer cells?

Answer 17

Promotes MHC Class 1 expression and cell division

Question 18

Cytokine therapy can be used in the treatment of cancer. Describe how IL-2 affects cancer cells?

Answer 18

Promotes expansion of tumour specific T cells

Question 19

How can monoclonal antibodies be used to combat cancer?

Answer 19

Specific antibodies which target cancer cells directly and mediate tumour destruction can be used

Question 20

By what mechanisms can monoclonal antibodies kill tumour cells?

Answer 20

Induction of apoptosis
complement mediated cytotoxicity
Conjugated to toxin/isotope

Question 21

Ipilimumab is a cancer therapy which blocks the CTLA4 antigen. What is the normal role of CTLA4?

Answer 21

It is an off switch for cell growth and division

Question 22

When may CTLA4 by switched off physiologically?

Answer 22

In the gut when faced with a foreign ingested substance to prevent digestion of gut by lymphocytes

Question 23

Describe how tumour cells use PDL1 to evade the immune system?

Answer 23

When PDL1 on cancer cells binds to PD1 on T cells this forms a biochemical ‘shield’ which protects the tumour cells from destruction and often causes apoptosis on the T cell

Question 24

What are the available cell based therapies in the treatment of cancer?

Answer 24

Haematopoietic stem cells
tumour infiltrating t cells
dendritic cell vaccines
Natural killer cells
gamma delta t cells
virus specific T cells
genetically engineered T cells