Immune response to cancer Flashcards
What are neo-antigens?
Antigens which arise from somatic mutations which produce abnormal peptide proteins which are then expressed by MHC complexes on cells
What are viral antigens caused by?
Oncogenic viruses
What type of mutations are responsible for tumour antigens?
Driver mutations
How to tumours become resistant to CD8+ T cells?
By downregulating MHC class molecules or molecules involved in antigen processing in proteosome.
How do tumours inhibit T-cell activity?
through CTLA-4 and PD-1
Name some cells in which tumours can promote to activate a immuno-suppressive environment
T regs, Myeloid derived suppressor cells, tumour associated macrophages
How does CTLA-4 inhibit T cell activity?
By raising the stimulatory threshold or by inhibiting proliferation
CTLA-4 acts as an alternative receptor for which co-stimulatory signal?
B7
Why are anti-CTLA-4 antibodies used?
to inhibit T regulatory cells (they are expressed on t regs)
What does PD-L1 regulate?
Regulates the induction and maintenance of the peripheral tolerance and protects tissue from autoimmune attack
What does the interaction between PD-1 and PD-L1 regulate?
Inhibits the activity of effector CD8 T cells by suppression of cytokine production and cytotoxicity
How are MDSCs immunosuppressive functions mediated.
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
Explain adenosines function in immunosuppression.
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.
Where do monoclonal antibodies target which treat B cell tumours.
CD20 (Anti-CD20 monoclonal antibodies)
What are examples of monoclonal antibodies used to treat cancer?
Herceptin, avastin (VEGF)
What is adoptive T cell therapy often combined with?
Combined with administration of T cell stimulating cytokines such as interleukin-2 (IL-2) and traditional chemotherapy
Describe the CAR structure which are currently in use.
CARs currently in use have a single chain antibody-like extracellular portion with both heavy-and light-chain variable domains.
Give an example of a adverse effect of CAR T cells.
Cytokine release syndrome (CRS)
Give an example of an immune checkpoint inhibitor.
Pembrolizumab (Keytruda)
Which receptor does pembrolizumab bind?
PD-1 receptor
Which HPV types are responsible for almost 70% of cervical cancers.
HPV type 16 and 18
Which HPV types does cervarix block?
HPV types 16 and 18
