Cancer Immunology Flashcards
what is the difference between a cold and hot tumour
cold tumours use fibroblasts to block immune cell infiltration
hot tumours have immune cells within the tumour microenvironment
what are tumour associated macrophages (TAM)
macrophages that aid the tumour
what occurs when TAM’s release VEGF and define it
angiogenesis and lymphoangiogenesis
it is the development of new blood vessels
besides angiogenesis, how else do TAM’s aid the tumour
release enzymes that break barriers to aid metastasis
promote tumour growth
immune system suppression
what is the function of IDO
breaks down tryptophan in the tumour microenvironment
what is the function of tryptophan
used to build proteins for cell growth and fighting infection - aiding the immune system
how does IDO promote tumour cell growth
regulates tryptophan levels - reduces the fuel needed for the immune system leading to:
- suppression of effector T-cells
- promotion of T-reg cells
outline steps 4-7 of the cancer-immunity cycle
4 - trafficking of T-cells to tumours (CTL’s)
5 - infiltration of T-cells into tumour and stroma
6 - recognition of cancer by T-cells
7 - cancer death
outline steps 1-3 of the cancer-immune cycle
1 - release of cancer cell antigens (cancer death)
2 - cancer antigen presentation (DC’s/APC’s)
3 - priming and activation (APC’s/T-cells)
in the cancer-immunity cycle, after infiltration of T-cells in the stroma, what happens before the T-cells recognise cancer cells
there is an accumulation of T-cells in the stroma
they then interact with immune cells
this leads to the T-cells to enter a maintained effector state and function
how do tumour cells prevent being killed by T-cells when bound
they express PDL-1 which activates PD-1 on T-cells
PD1 is an inhibitory receptor so it blocks the T-cells own function
how may anti-CTLA-4 antibodies work
by inhibiting an inhibitory receptor - CTLA-4 - on T-regulatory cells, disinhibiting the immune system
what is rituximab
an anti-hCD20 monoclonal antibody
first monoclonal antibody (mAb) used to treat cancer
what is the mechanism of action of rituximab
rituximab binds to CD-20 on tumour cells and Fc-receptors on macrophages - leads to cell tumour cell death
how have tumour cells developed resistance to rituximab
tumour cells express a receptor (CD32B)
when rituximab binds CD-20, the Fc tail of rituximab binds to CD32B instead
the tumour then absorbs the antibody - preventing macrophage signalling
