Role of the Immune System in Cancer Flashcards
What is cancer?
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
What is the most mutated cell?
Melanoma (from exposure to UV light)
What is immunosurveillance?
Process by which cells of the immune system look for and recongise foreign pathogen or (pre)cancerous cells
What are the three E’s of immunity and cancer?
Elimination
Equilibrium
Escape
What happens in the Elimination of Cancer cells?
Innate and Adaptive immunity cells recongise the cell and target it, reducing the numbers
Why does Equilibrium occur when dealing with cancer cells?
Tumour cell mutates and gain gentetic mutations, immune cells adapt to the changes to keep the cancer cell at a constant (preventing growth)
Why does escape occur when dealing with cancer cells?
Tumour cells mutated to the point immune cells are not able to keep up and the tumor cell can grow and increase its numbers
Why is the presence of T lymphocyte in cancer cells good?
Due to ability to produce IFNy and kill the cancer cells
- CD8+ CTL and Nk cells are important mediators of the anti tumor response
How does lymphoctyes see a tumour if it is self?
- 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
What is the Neoantigens?
Novel proteins that the immune system can see
What is the Tumour associated antigens (TAA)?
Antigens prefernetially expressed by a tumour (also expressed elsewhere)
What is the TUmour specific antigens (TSA)?
Antigens that are only expressed by the tumour
What happens if the tumour mutates more?
The greater the chances of the tumour being seen by the immune system
How can neoantigens be used?
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
How does immunosureillance fail?
Lack of inflammation (no signal 2)
Lack of local suppression
Why does no signal 2 cause immunosureillance to fail?
T cells might not be switched on adequetely
Why would signal 2 be missing?
Signal 2 ligands need DAMPs/PAMPs to be expressed at high high levels
What is Coley’s toxin?
An adjuvant to help the immune system to respond
- Mix of bacteria
How can signal 2 enhance tumour therapy?
- Signal 1 orginates from the tumou r
- Signal 2 supplied artificially with an activating antibody to co-stimulatory receptors
What receptor switches T cells off?
CTLA-4
What factors are used to engineer antibodies in making them agnoists or antagonists?
- Istotype
- Epitope
- Interaction with Fc receptors
- Differences between mice and humans
What signal does CTLA-4 produce and what does it bind to?
Negative
Binds to B7
What usage did CTLA-4 for have?
Develoing an antagonist anti-CTLA-4 mAb to prevent it binding
Why does tumour cells get bigger?
Inflammation as immune cells flooded into the tumour cells
Why does tumour cells switch off CD8+ T cells?
Due to the tumour cell receptor PD-L1 binding to the T cell receptor PD-1
What does Nivolumab do in the bdoy?
Antibody that blocks PD-1
What are check point inhibitors?
Nivolumbat (blocking PD-1) and ipilimumab (blocking CTLA-4) used together
How can Rituximab be used?
Reduce antibody response when directed agaianst self (e.g autoimmune disease)
- Used to remove all B cells and eradicate B cell tumours
What cell express CD20 on the surface which is a surface expressed TAA?
CD20
What is rituximab’s function?
1) Antibody dependent cellular cytotoxicity (NK killing)
2) Complement damage
3) Direct cell death
4) Antibody depdent phagocytosis (macrophage)
What are CAR T cells?
Receptors that have had antibodies that are known to see TAA/TSA on TCR and express it in patient’s own T cells
What are the 1st generation of CAR T Cells?
Fab region of anti CD19 fused to signalling component of CD3
What are the 2nd and 3rd generations of CAR T cells
Incorporating cytoplasmic tails from co-stimulation
Where can CD19 be found?
On the surface of B cells
What signals do the 2nd and 3rd generations produces when coming into contact with CD19?
Signal 1 and 2
What signal does the 1st generation CAR produce when seeing CD19?
Signal 1
What does CAR T cells bypass?
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
How is CAR T cells used?
Uses the antigen-specific region of an antibody with the signalling components from a TCR
What is the meaning of CAR T cell?
Chimeric Antigen Receptor
