Role of the Immune System in Cancer

Question 1

What is cancer?

Answer 1

Altered self
- No longer responds to checks and homeostasis
- Starts from a mutated cell which dictates tumour type (E.g lung cell would be lung cancer)
- Cancers are clonal

Question 2

What is the most mutated cell?

Answer 2

Melanoma (from exposure to UV light)

Question 3

What is immunosurveillance?

Answer 3

Process by which cells of the immune system look for and recongise foreign pathogen or (pre)cancerous cells

Question 4

What are the three E’s of immunity and cancer?

Answer 4

Elimination
Equilibrium
Escape

Question 5

What happens in the Elimination of Cancer cells?

Answer 5

Innate and Adaptive immunity cells recongise the cell and target it, reducing the numbers

Question 6

Why does Equilibrium occur when dealing with cancer cells?

Answer 6

Tumour cell mutates and gain gentetic mutations, immune cells adapt to the changes to keep the cancer cell at a constant (preventing growth)

Question 7

Why does escape occur when dealing with cancer cells?

Answer 7

Tumour cells mutated to the point immune cells are not able to keep up and the tumor cell can grow and increase its numbers

Question 8

Why is the presence of T lymphocyte in cancer cells good?

Answer 8

Due to ability to produce IFNy and kill the cancer cells
- CD8+ CTL and Nk cells are important mediators of the anti tumor response

Question 9

How does lymphoctyes see a tumour if it is self?

Answer 9

• Safe reactive T and B cells are deleted in the thymus/bone marrow
• Views the virus as an infection if the tumour is driven by a virus

Question 10

What is the Neoantigens?

Answer 10

Novel proteins that the immune system can see

Question 11

What is the Tumour associated antigens (TAA)?

Answer 11

Antigens prefernetially expressed by a tumour (also expressed elsewhere)

Question 12

What is the TUmour specific antigens (TSA)?

Answer 12

Antigens that are only expressed by the tumour

Question 13

What happens if the tumour mutates more?

Answer 13

The greater the chances of the tumour being seen by the immune system

Question 14

How can neoantigens be used?

Answer 14

If they contain peptides and bind with MHC, they can be presented to T cells and activate them to stimulate a response against a tumour

Question 15

How does immunosureillance fail?

Answer 15

Lack of inflammation (no signal 2)
Lack of local suppression

Question 16

Why does no signal 2 cause immunosureillance to fail?

Answer 16

T cells might not be switched on adequetely

Question 17

Why would signal 2 be missing?

Answer 17

Signal 2 ligands need DAMPs/PAMPs to be expressed at high high levels

Question 18

What is Coley’s toxin?

Answer 18

An adjuvant to help the immune system to respond
- Mix of bacteria

Question 19

How can signal 2 enhance tumour therapy?

Answer 19

• Signal 1 orginates from the tumou r
• Signal 2 supplied artificially with an activating antibody to co-stimulatory receptors

Question 20

What receptor switches T cells off?

Answer 20

CTLA-4

Question 21

What factors are used to engineer antibodies in making them agnoists or antagonists?

Answer 21

• Istotype
• Epitope
• Interaction with Fc receptors
• Differences between mice and humans

Question 22

What signal does CTLA-4 produce and what does it bind to?

Answer 22

Negative

Binds to B7

Question 23

What usage did CTLA-4 for have?

Answer 23

Develoing an antagonist anti-CTLA-4 mAb to prevent it binding

Question 24

Why does tumour cells get bigger?

Answer 24

Inflammation as immune cells flooded into the tumour cells

Question 25

Why does tumour cells switch off CD8+ T cells?

Answer 25

Due to the tumour cell receptor PD-L1 binding to the T cell receptor PD-1

Question 26

What does Nivolumab do in the bdoy?

Answer 26

Antibody that blocks PD-1

Question 27

What are check point inhibitors?

Answer 27

Nivolumbat (blocking PD-1) and ipilimumab (blocking CTLA-4) used together

Question 28

How can Rituximab be used?

Answer 28

Reduce antibody response when directed agaianst self (e.g autoimmune disease) - Used to remove all B cells and eradicate B cell tumours

Question 29

What cell express CD20 on the surface which is a surface expressed TAA?

Answer 29

CD20

Question 30

What is rituximab's function?

Answer 30

1) Antibody dependent cellular cytotoxicity (NK killing) 2) Complement damage 3) Direct cell death 4) Antibody depdent phagocytosis (macrophage)

Question 31

What are CAR T cells?

Answer 31

Receptors that have had antibodies that are known to see TAA/TSA on TCR and express it in patient's own T cells

Question 32

What are the 1st generation of CAR T Cells?

Answer 32

Fab region of anti CD19 fused to signalling component of CD3

Question 33

What are the 2nd and 3rd generations of CAR T cells

Answer 33

Incorporating cytoplasmic tails from co-stimulation

Question 34

Where can CD19 be found?

Answer 34

On the surface of B cells

Question 35

What signals do the 2nd and 3rd generations produces when coming into contact with CD19?

Answer 35

Signal 1 and 2

Question 36

What signal does the 1st generation CAR produce when seeing CD19?

Answer 36

Signal 1

Question 37

What does CAR T cells bypass?

Answer 37

1) Requirement for MHC on the tumour (TCR is restricted by MHC so tumour could downregulate it) 2) Low TCR affinity for the MHC/peptide complex 3) Requirement for co-stimulation

Question 38

How is CAR T cells used?

Answer 38

Uses the antigen-specific region of an antibody with the signalling components from a TCR

Question 39

What is the meaning of CAR T cell?

Answer 39

Chimeric Antigen Receptor