Cancer And Immune System Flashcards
How do tumours subvert adaptive immune response? 4
Induction of T cell anergy/ exhaustion
Suppress effector functions and apoptosis
Induction, maintenance and expansion
Recruitment
How do tumours subvert innate immune response? 7
Immune suppression by iNos and ARG1 Expansion and immune suppression M2 polarisation and immune suppression Inhibition of DC activation Population expansion Recruitment and immune suppression Polarisation to pro tumour phenotype
3 facts about cd8+ cytotoxic T cells
When exposed to infected or dysfunctional somatic cells, they release perforins, granulocytes and granzymes
2 signal activation
Effector function needs regulation
What do CD4 th1 cells do
Enhancers of CTL effector response and macrophage activation
What is T cell exhaustion
An unresponsive state defined by loss of effector functions
What is T cell anergy?
An induced non responsive state as part of peripheral tolerance- so you don’t get self reactive T cells
What do exhausted T cells express?
Inhibitory receptors
Characteristic low production from anergic T cells
Il2
What can tumour cells produce to escape immune response? 6
Ido Tgfb Il10 Pge2 Pdl1 Ctla4
What’s the drug that targets CTLA4?
Yervoy - ipilumumab
What has yervoy been approved in?
Unresectable or metastatic melanoma
What kind of drug is yervoy?
mAB- recombinant human IgG
6 immunoregulatory pathways in cancer
Chronic ag stimulation Defective cd4 help Inhibitory receptors Suppressive cells Soluble mediators Metabolic checkpoint and hypoxia
4 types of mAbs
Murine
Chimeric
Humanised
Human
Murine mAb
Entirely murine AA
Chimeric mAB
Human constant (C) and murine variable (V) regions
humanised mAB
Murine CDRs
Human mAB
Entirely human aas
Why are translation between human and mouse FcR responses complex?
Due to FcR structural diversity, functional differences and expression profiles of human FcRs
Fc optimised mAb production 6 steps
Hybridoma cDna isolation Resolution of variable sequence IgG optimisation mAB production and purification Binding test Treatment of humanised FcR mice
What does Fak do?
Nuclear fak drives expression of Ccl5 and other chemokines in SCC tumour cells
Ccl5 promotes TReg recruitment/retention
TReg suppresses antitumour CD8+ cells
