The role of the immune system in cancer Flashcards
What are the three stages of cancer and immune system? [3]
Elimination (immnune system kills cancer)
Equilibrium (cancer and immune system are in stale-mate
Escape: (cell evades immunosurveillance)
What are the three phenotypes of cancer [3]
Immune-desert tumour: There is a tumour, but no T Cell army is present to mount an attack.
Inflamed tumour: Inhibition of various inflammatory molecules to avoid destruction and create an ideal environment
Immnune-excluded tumour: high immune cell density in the outer invasive margin and low density in the core
Describe what checkpoint inhibition is [1]
State two key molecules influential in checkpoint inhibition [2]
Checkpoint inhibitors: take the brakes off the immune system; checkpoints inhibits the stop sign that a cancer cell usually presents to immune cells
Checkpoints (caused by)
PD1 Programmed Death Receptor 1
CTLA-4 Cytotoxic T-Lymphocyte Associated protein 4
Explain the role of the PD1 checkpoint [2]
PD1 regulates T cell activation through binding with the ligands programmed death-ligand 1 (PDL1) and programmed cell death 1 ligand 2 (PDL2)
This inhibits T cell proliferation and survival: helps prevent the immune system from attacking itself
Explain the influence of cancer cells on PD1 checkpoint
Cancer cell can turn off the PD-1 pathway:
.
If PDL1 or PDL2 are expressed within the tumour microenvironment (TME), the ligands can bind to PD1, terminating TCR signalling and reducing the activation of T cells.
Which drugs bind to PD-L1? [3]
Atezolizumab
Durvalumab
Avelumab
Which drugs bind to PD-1? [2]
Pembrolizumab
Nivolumab
Explain the role of CTLA-4 [1]
What happens if CTLA-4 is inhibited? [1]
CTLA-4 suppressed T cell activation and inhibits cell function; plays a role in T-cell priming
Inhibiting CTLA-4 ”takes the breaks off” the immune system
Name two drugs that inhibit CTLA-4
Ipilimubab
Tremelimubab
What is the difference between chimeric and humanised monoclonal antibodies? [2]
- chimeric: Monoclonal antibody with a large stretch of non-human proteins
- humanized: Monoclonal antibody coupled with a human Ig backbone
What are the three ways that monoclonal antibodies are broadly used? [3]
Complement mediated lysis: unconjugated
Immunotoxins: Coupled to toxin
Radioimmunoconjugates: Coupled to radioisotopes
Give an example that is a chimeric monoclonal antibody used for treating B-Lymphomas [1]
What is the target? [2]
Rituximab: targets CD20 on malignant B-cells and CD3 on normal T cells
Together enhance cytotoxicity
What are Chimeric antigen receptors? [1]
Chimeric antigen receptors (CARs): are recombinant receptors for antigens which redirect the specificity and function of T lymphocytes and/or other immune cells in a single molecule.
(Chimeric antigen receptors: on the surface we have the antibody components so the T cells are recognised by the antigen on the tumour cells, and 2nd and 3rd generation CARs have additional costimulatory molecules to enhance the immune response)
Explain the mechanism of how chimeric antigen receptor treatment occurs [3]
Take T cells
Retrovirally transfect them to be able to express the chimeric antigen whereby you have the antibody on the surface linked into the molecule that activates the T cell
(T cells are removed from a cancer patient and modified so they express receptor specific to the patient’s cancer, then are reintroduced to patient)
T cell then recognises the tumour cell and that activated tumour cell kills off these cells
Give an example of CAR-T drug for targetting large B-cell lymphoma? [1]
What is the drug target? [1]
Tisagenlecleucel (Kymriah)
CAR-T Cell targeting CD19
