Cancer Flashcards
what is cancer?
group of diseases characterized by
- uncontrolled cell growth
- invasion of cells into surrounding tissue
- metastasis
hallmarks of cancer
- sustaining proliferative signalling
- evading growth suppressors
- activating invasion and metastasis
- enabling replicative immortality
- inducing angiogenesis
- resisting cell death
what causes cancers?
- genetic mutations
> heritable + lifestyle factors - chemical carcinogens
- radiation
- viral or bacterial infections
how do genetic mutation cause cancer?
- inactivation of tumor suppressors “brakes”
- alteration of DNA repair gene function “mechanic”
- overexpression of oncogenes “gas pedal”
NOTE: normal cells have balance of growth and promoting and suppressing signals
emerging hallmarks of cancer
- deregulating cellular energetics
- avoiding immune destruction
- tumor-promoting inflammation
- genome instability and mutation
________ ________ _______ indicate poor prognosis
tumor associated macrophages
tumor infiltrating lymphocytes
CD8+ T cells
TAAs
tumor associated antigens
- normal proteins that antibodies see all the time; not limited to tumor
- overexpressed in cancer
- failed to elicit complete tolerance by immune system
- could be an antigen expressed during embryonic proteins (reactivated proteins after development (was turned off, now reactivated so immune system sees it as new)
TSAs
tumor specific antigens
- specific to tumor itself
- structurally novel proteins
- ex: translocation proteins, mutated alleles, viral proteins
three E’s of immunoediting
- elimination
- equilibrium
- escape
immunoevasion strategies
- hide identity
- avoid apoptosis
- induce complement
- neutralize complement
- inactivate immunocytes
how do tumors hide their identity?
- antigen negative variants through DNA dysregulation or downregulation via gene promoter methylation
- repressing MHCI transcription = prevents TSA/TAA antigen presentation on cell surface
how do tumor cells avoid apoptosis by NK cells?
NK cells have killer immunoglobulin-like receptor = KIR
- inhibitory receptor that is inactive when UNbound
- binding MHC I = active receptor = inhibited attack (cell safe)
- tumor cells express just enough (1/6) so NKs don’t attack = decreases costim expression of CD80/86 on APC
two ways that tumors can induce immunocyte apoptosis
- having mutations that inhibit downstream signalling (altered gene/FasR activated by T cell but downstream disruption that will not allow apoptosis to occur)
- releasing soluble FasL to bind to Fas receptors of T cells nearby to cause cell death
how do cancer cells neutralize complement?
- cancer pts = high levels of anti-tumor Abs (vulnerable to complement)
- LAN1-rat CD59 evades complement induced lysis by MAC = increased tumor growth
> over expresses CD59/MIRL/protectin
