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Flashcards in cancer immunology Deck (9)
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1
Q

hallmark of cancer

A

ability to evade immune detection

2
Q

anti tumour immunity

A

is specific
tumours have antigens that are recognised by immune cells
antigens derived from self molecules that escape T cell tolerance: the cancer/testis antigen e.g MAGE
oncofecal antigen e.g Ca125
differentiation antigens- tyrosinase in melonoma

neoantigens derived from genes mutated in cancer such as p53 and Ras.
cancer specific alterations of proteins: MUC post translationally modified, abberent splice products
Antibody response - NY-ESO-1 antigen generates antibody and T cell response

3
Q

cancer immunoediting: Three Es

A

Elimination: immune system has the upper hand, cancer cells unable to proliferate, recognised by lymphocytes which destroy them

equilibrium: ‘cult cancer’ mutations occur within cells that make them resistant to killing/undetectable. Growth still controlled by immune system
escape: cancer cells escape immune control and proliferate, only now is the cancer clinically detectable

4
Q

cancer evades immune killing

A

mutation in B2 microglobulin gene causes loss of MHCI expression by tumour cells, so CD8 cells cannot see and attack them
NK cells can recognise and kill cells lacking MHC
they have a killer inhibitory signal - inhibited by MHC
when no MHC = no binding = signals to kill cell

cancer cells lose antigens, secrete immunosuppressive cytokines, metabolically compete with cells and induce immune checkpoints

5
Q

E2F

A

drives cell cycle genes, mutated in most cancer, proliferation increased. Also drives expression of NKG2D ligand. A highly proliferating cell will express lots of NKG2D ligand
bind to NKG2D receptor on NK cells - activates killing

6
Q

immune checkpoints

A

naturally occuring feedback inhibitors of the immune system
allows immune system to dampen responses when threat has cleared
T cell activation causes killing of infected cells, cytokine release ad then initiation of immune checkpoint molecule expression e.g PDI.
The pro inflammatory cytokine IFN-y produced by T cells induces expression of PD-L1 on tumour cells.
Mutations on tumour cells could also cause aberrant expression of PD-L1.
PD1 and PD-L1 interaction exhausts the T cell and it dies by apoptosis, and it cannot kill anymore cells, so the cancer manages to avoid killing

7
Q

Treatment for cancer: immune checkpoint blockade

A

blocking the PD1-PD-L1 interaction using PD1 antibodies

8
Q

antibody based targeting of tumour cells

A

retuximab - anti CD20
herceptin - anti HER2
chimeric, mouse variable region fused to human IgG Fc portion
complement mediated cytotoxicity kills cells coated with antibody

9
Q

retargeting T cell activity using CART cells

A

replace T cell receptor with antigen receptor based on an scFv antibody.
can recognise antigens directly
T cells bypass normal safeguard for self reactivity - life threatening