L14 - Tumour microenvironment Flashcards
(17 cards)
name 5 hallmarks of cancer
Susatining proliferatiove growth
Avoiding immune detection
Tumor-promoting inflammation
Inducing or assessing vascalture
activating invasion + Metastasis
what are mos cancers derive from and why
epithelial cells - barrier beytween inside and outside of our bodoies
= exposed to mutagens and divide constantly to replace lost cells
what are tunmors made of
mix of cancer and non-cancer (stromal) cells
= ‘wound that never heals’
what are fibroblasts
produce Extracellular matrix in connective tissue
create ECM to support other cell types
what do cancer asociated fibroblasts (CAFs) do in hypoxic environments
produce growth and cytokines
= promote cancer cells growth (EGF)
= recruit immune cells
= recruit endothelial cells for blood vessel formation (VEGF)
= alter ECM to promote growth and spreading
name the cytokine produce by Cancer asociated Fibroblasts (CAFs) that can cause immune suppression and promote cancer movement
TGF-β
= tumour growth factor
= junctions between cells wekaned –> movement easier
name a growth factor produce by CAFs
EGF
= epidermal growth factor
name the factor produce by CAFs to induce new blood vessel formation
VEGF
= Vascular endothelial growth factor
what growth factors and cytokines do Tumour-ascoaited macrophages produce
macrophages promote inflammation —> tissue resident or recruited blood monocytes
- EGF = growth factor
- IL-10 and TGF-β = suppress T-cells
- VEGF = form blood vessels
why do we want to target macrophages as a cancer drug target
macrophages are abundant in tumors and cause inflammation/damage
what do macrophages require to proliferate
CSF-1
= binds to macrophage receptor promoting proliferation
cancer cells can produce this
= inhibition of receptor can be a cancer therapy
name the cytokine that dirves T-cell proliferation
IL-2
what do regulatory T-cells (Tregs) produce to suppress cytotoxic T-cells proliferation
IL-10 and TGFβ
= prevent activation and proliferation
name the enzyme released by CD8+/NK cells to kill infected cells
Perforin
= forms pores in cell membrane
normal functions of Tregs
suppress T-cells = IL-10 + TGFβ
supress autoimmunity and hypersensitivity –> peripheral tolerance
what do cancer cells produce to suppress CD8+/cytotoxic T cells
PD-1 and CTLA-4
- PD-1 binds to PDL = inhibitory signals shuts down P13/akt pathway
- CTLA-4 = suppress IL-2 production and cell cycle progression
- Tregs use this aswell
= both inactiavte and sipress T-cells activation and effector functions
name some targets for antibodies in cancer treatment to enhance CD8/cytotxcic T cells
PD-1 and CTLA-4 receptors
= prevents immune suppression by cancer cells
