Role Of The Immune System In Cancer Flashcards
3 states of immune system-cancer interaction
Elimination
Equilibrium
Escape
Process of cancer elimination by the immune system
Release of cancer cell antigens -> antigen presentation -> priming and activating immune cells -> trafficking T cells to tumours -> infiltration of T cells into tumours -> recognition of cancer cells by T cells -> killing of cancer cells
Cancer-immune system equilibrium
Cancer cells present but held in place by immune system
3 main groups of immune system escaping tumours
Immuno excluded tumours
Immune desert tumours
Inflamed tumours
How do inflamed tumours escape the immune system
Immune cells present but don’t kill cancer due to other factors of tumour, immune cells, or tumour microenvironment
How do immune secluded tumours evade the immune system
Immune cells can’t reach tumour, usually due to manipulation of tumour microenvironment
How do immune desert tumours evade the immune system
No immune cells, often due to lack of antigens, lack of APCs, or tumour down regulating immune system
How does immunotherapy augment/restore immune system function
Killing cancer cells releases contents including antigens
Stimulate APCs
Artificially give antigens via vaccination
Incr T cell number
Make it easier for T cells to infiltrate tumour
Remove cancer cell protection and environment/immune system manipulation
Checkpoint inhibition immunotherapy
Block checkpoint inhibition proteins to stop immune system being switched off
Which inhibitory immune system checkpoint receptor is most commonly targeted in cancer therapy
PD1
What is the effect of cancer cells binding to PD1 receptors on immune cellso
Turn off immune system
What causes upregulation of inhibitory checkpoints on T cells
Long term engagement of T cells
How can cancer cells switching off immune responses via binding to PD1 be prevented
Drugs targeting PD1 receptors on T cells and PD1 ligands on cancer cells
What do atezolizumab, durvalumab, and avelumab target
PD1 ligands on cancer cells
What do pembrolizumab and nivolumab target
PD1 receptors on T cells
How are monoclonal antibodies from mice altered so humans don’t develop mouse antibodies
Chimerised or humanised
What is a chimeric antibody
Monoclonal antibody with a large stretch of non human proteins
What is a humanised antibody
Monoclonal antibody coupled with a human Ig backbone
What can monoclonal antibodies be coupled to
Toxins
Radioisotopes
What is a monoclonal antibody coupled to a toxin or radioisotope called
Toxin - Immunotoxin
Radioisotope - radioimmunoconjugate
How do unconjugated monoclonal antibodies target cancer cells
Complement mediated lysis
How do immunotoxins target cancer cells
Bind to receptors, are internalised by tumour cells, and inhibit protein synthesis
How do radioimmunoconjugates target cancer cells
Bind to cell surface receptors, translocate into cells, and damage DNA
What is the type of toxin or radioisotope conjugated to a monoclonal antibody chosen based on
Cancer type
What type of drug is rituximab and what does it target
Monoclonal antibody
CD20
Which type of cancer does CD20 present on the cell surface of
B lymphomas
How does blinatumomab force immune system recognition of malignant B cells
Targets CD19 on malignant B cells and CD3 on T cells simultaneously bringing them together
What is CAR
Chimeric antigen receptor
What is kymriah/tisagenlecleucel
CAR T cell targeting CD19 on B cell lymphomas
What viruses can cause cancer
Hep B and C
Human T lymphotropic virus
HPV
Kaposis sarcoma associated herpesvirus
Merkle cell polyomavirus
Epstein Barr virus
Is immunotherapy most effective in cancers with high or low neoantigen formation
Low
What age is HPV vaccine given
12-13 yrs, 2nd dose 6-24mo after first
How can changes to the extracellular matrix caused by tumour cells decrease immune response
Prevent immune cell infiltration
Adoptive cell transfer
Tumour excised, immune cells cultures and assayed for tumour recognition, tumour recognising cells expanded and reinfused
