Cancer

Question 1

what is cancer?

Answer 1

group of diseases characterized by
- uncontrolled cell growth
- invasion of cells into surrounding tissue
- metastasis

Question 2

hallmarks of cancer

Answer 2

• sustaining proliferative signalling
• evading growth suppressors
• activating invasion and metastasis
• enabling replicative immortality
• inducing angiogenesis
• resisting cell death

Question 3

what causes cancers?

Answer 3

• genetic mutations
  > heritable + lifestyle factors
• chemical carcinogens
• radiation
• viral or bacterial infections

Question 4

how do genetic mutation cause cancer?

Answer 4

• 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

Question 5

emerging hallmarks of cancer

Answer 5

• deregulating cellular energetics
• avoiding immune destruction
• tumor-promoting inflammation
• genome instability and mutation

Question 6

________ ________ _______ indicate poor prognosis

Answer 6

tumor associated macrophages

Question 7

tumor infiltrating lymphocytes

Answer 7

CD8+ T cells

Question 8

TAAs

Answer 8

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)

Question 9

TSAs

Answer 9

tumor specific antigens
- specific to tumor itself
- structurally novel proteins
- ex: translocation proteins, mutated alleles, viral proteins

Question 10

three E’s of immunoediting

Answer 10

• elimination
• equilibrium
• escape

Question 11

immunoevasion strategies

Answer 11

• hide identity
• avoid apoptosis
• induce complement
• neutralize complement
• inactivate immunocytes

Question 12

how do tumors hide their identity?

Answer 12

• antigen negative variants through DNA dysregulation or downregulation via gene promoter methylation
• repressing MHCI transcription = prevents TSA/TAA antigen presentation on cell surface

Question 13

how do tumor cells avoid apoptosis by NK cells?

Answer 13

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

Question 14

two ways that tumors can induce immunocyte apoptosis

Answer 14

• 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

Question 15

how do cancer cells neutralize complement?

Answer 15

• 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

Question 16

how do tumor cells inactivate immunocytes?

Answer 16

• tumor cells attract Treg cells via chemokine CCL22 (CCR4 of Tregs bind CCL22)
  = tumors have increased Tregs than normal cells
• Tregs suppress Th cells = cytotoxic T cells dysfunctional