Week 14 Flashcards
What are the ‘hallmarks’ of cancer?
Stimulate their own growth Ignore growth-inhibiting isnglas Avoid death by apoptosis Angiogenesis Metastasis Constant proliferation Evade and outrun immune response
What are the 4 key cell types involved in recognising and eliminating tumours?
CD4+
NK
γδ T cells
CD8+ (CTLs)
What are the 5 key mechanisms by which tumour avoid immune recognition?
Low immunogenicity Tumour treated as self-Ag Antigenic modulation Tumour-induced immune suppression Tumour-induced privileged site
How do tumours to avoid immune recognition via low immunogenicity?
No peptide-MHC ligand - appear ‘normal’
No adhesion molecules
No co-stimulatory molecules - can’t activate naive T cells
How do tumours to avoid immune recognition via antigenic modulation?
Can initially express Ags to which the immune system respond, but lose them through antibody-induced internalisation or antigenic variation, meaning there is selection of the Ag-loss variation
How do tumours to avoid immune recognition via tumour-induced immune suppression?
Tumour cells can secrete factors that directly suppress immune responses eg. TGF-β, IL-10, IDO, PD-L1
How do tumours to avoid immune recognition via tumour-induced privileged sites?
Factors secreted by tumour cells create a physical barrier to the immune system
The phenotype of lymphocytic infiltrates in tumours is a key factor in determining clinical outcome. Which types were predominantly associated with good outcome?
CD8 - CTLs essential for tumour destruction
Th1 - facilitate Ag presentation
The phenotype of lymphocytic infiltrates in tumours is a key factor in determining clinical outcome. Which types were predominantly associated with poor outcome?
Th2 Treg Inhibit CTL function Support B cell proliferation May promote anti-inflammatory response
Sipuleucel-T was the first FDA approved anti-tumour vaccine. How does it work?
Prostatic acid phosphatase (PAP) is found in increased amounts in prostate cancer pt.s
Monocytes isolated from prostate cancer pt.s
They are cultured w/ GM-CSF/PAP fusion protein
GM-CSF induces the monocytes to => DCs, PAP is internalised and presented by MHC II
Activated DCs infused back into the pt.s, present PAP to naive T cells
What effect does GM-CSF have on monocytes?
Induces monocytes to mature in DCs
What is adoptive cell transfer (ACT)?
Lymphocytes with anti-caner properties are grown in vitro - can expand to larger no.s without tolerating influences of the body.
Then given to pt.s - they may have been manipulated so their tumour microenvironment is free of suppressive factors that could impact the lymphocytes
What are CAR T cells?
Chimeric Ag receptor T cells
= T cells (usually from the pt) who have had synthetically constricted CAR TCRs added. These synthetic TCRs bind to a specific Ag on the tumour
They may also have been manipulated to have other factors that allow them to deal with the suppressive tumour microenvironment, eg. additional costimulatory receptors
What are the potential side effects of CAR T cell therapy?
Cytokine release syndrome - large no. of tumour cell death means ++ cytokines released. Begins 1-5 days after infusion with high fevers, can be deadly
Neurological toxicity - CART cells migrate to the CNS, can be found in CSF
CAR T cell therapy can result in CRS. How can this be treated?
Immune suppressants and IL-6 blockade
