Reza/Raja quiz 10 Flashcards
___: it is a characteristic of nutrient competition, low ph, limited oxygen and accumulation of metabolites
-such conditions result in immunosuppressive or tolergenic phenotypes of immune cells that encourage metabolism to rely on _____and ____
- tumor microenvironment
2.oxidative phosphorylation and fatty oxidation
tumor microenvironment accelerate T effector cell exhaustion and increase immune checkpoint expression, this promotes differentiation and accumulation of ____
Treg, M2-like macrophages and myeloid-derived dendritic cells (MDSC)
tumor microenvironement also produces unique subsets of myeloid cells known as _____and ____
tumor associated dendritic cells (TADCs) and tumor associated neutrophils (TANS)
tumor microenvironment nutrient deprivation includes?
decrease glucose, decrease glutamine, decrease arginine
tumor microenvironment metabolite accumulation includes?
increase lactate and increase kynurenine
tumor microenvironment includes ____ and ____
acidity and hypoxia
activated T cells: lead to an increase in glycolytic and glutaminolytic metabolism by using ___ for ATP production and biosynthesis for clonal expansion
aerobic glycolysis
regulatory T cells (Tregs) rely on ___ and ___ to support their survival and differentiation
oxphosphorylation and fatty oxidation
macrophages reprogram their metabolism in response to tumor microenvironment through ____ while maintaining function of cytokine production
glycolysis, fatty acid synthase and altered nitrogen cycle metabolism
tumor associated macrophages (TAM) are categorized into ___ and __ phenotypes
M1 like and M2 like
____: increase inflammatory phenotype, use glycolysis, fatty acid synthase and amino acid metabolism
M1 like
___: have suppressive phenotype, using fatty acid oxidation and TCA cycle
M2 like
neutrophils normally are purely glycolytic to support ___and __-
ATP generation and microbial killing
neutrophils in cancer it is considered glucose restricted conditions, neutrophils engage in oxidative mitochondrial metabolism and fatty acid oxidation to support NADPH oxidase dependent ___
ROS production
the increase in glycolytic activity of cancer cells combined with poor vascular exchange results in: ____
-decrease glucose in TME
-limit in T cell expansion
-decrease in effector function through competition or altered apoptosis or eventual exhaustion
immune checkpoint blockade is an immune targeted strategy used clinically for cancer, an increase in expression of checkpoint receptors is due to ____ in TME, engagement of receptors decrease glycolysis and increase fatty acid oxidation
low glucose, acidity or lactate
antibodies against immune checkpoint bloackade receptors restores?
glycolysis
most promising therapy: immune checkpoint blockade (ICB) restores ____ metabolism and effector function in TILs
anabolic