Cancer Immunology Flashcards
two ways that cancer evades immune system
guards vs. cloak
cloak methods
intrinsic factors- antigen loss of MHC loss, secrete immunosppressive cytokines (IL-10); EXPRESSION OF PDL-1 THAT ALTER T CELL FUNCTION
guards
extrinsic factors- geographic barriers and suppressing suppressors or regulatory immune cells (TAMs and MDSCs)
3 ways to drive the immune response
- T cell receptor interacting with MHC 2. CD28:B7 3. CTLA-4: B7 and PD1: PDL1
how do we upregulate the first one (the t cell receptor interacting with MHC)
CAR therapies, vaccines, adoptive T cell therapies
how do we upregulate the CD28:B7?
agonist antibodies
how do we upregulate ctla-4 and PD1?
checkpoint blockade
toxicity profile for ipi
common: colitis and rash which we can stop with high dose steroids
infrequent: hepatitis and hypophysitis (decrease in size of pituitary) and these are untreatable
kinetics of ipi
gets worse before it gets better
normally scan at week 18
alot of heterogeneity with response
toxicity profiles for pd1 blocker
pneumonitis is more common; diarrhea and rash much less compared to ipi
abscopal effect (unexpected benefit)
being on combined immunotherapy, if you radiate 1 tumor, you get a systemic response to radiation even in areas not radiated
unexpected toxicity
hepatotoxicity when you combine ipi with some other drug