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Health Studies > Reza/Raja quiz 10 > Flashcards

Reza/Raja quiz 10 Flashcards

1
Q

___: 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 ____

A
  1. tumor microenvironment
    2.oxidative phosphorylation and fatty oxidation
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2
Q

tumor microenvironment accelerate T effector cell exhaustion and increase immune checkpoint expression, this promotes differentiation and accumulation of ____

A

Treg, M2-like macrophages and myeloid-derived dendritic cells (MDSC)

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3
Q

tumor microenvironement also produces unique subsets of myeloid cells known as _____and ____

A

tumor associated dendritic cells (TADCs) and tumor associated neutrophils (TANS)

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4
Q

tumor microenvironment nutrient deprivation includes?

A

decrease glucose, decrease glutamine, decrease arginine

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5
Q

tumor microenvironment metabolite accumulation includes?

A

increase lactate and increase kynurenine

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6
Q

tumor microenvironment includes ____ and ____

A

acidity and hypoxia

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7
Q

activated T cells: lead to an increase in glycolytic and glutaminolytic metabolism by using ___ for ATP production and biosynthesis for clonal expansion

A

aerobic glycolysis

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8
Q

regulatory T cells (Tregs) rely on ___ and ___ to support their survival and differentiation

A

oxphosphorylation and fatty oxidation

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9
Q

macrophages reprogram their metabolism in response to tumor microenvironment through ____ while maintaining function of cytokine production

A

glycolysis, fatty acid synthase and altered nitrogen cycle metabolism

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10
Q

tumor associated macrophages (TAM) are categorized into ___ and __ phenotypes

A

M1 like and M2 like

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11
Q

____: increase inflammatory phenotype, use glycolysis, fatty acid synthase and amino acid metabolism

A

M1 like

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12
Q

___: have suppressive phenotype, using fatty acid oxidation and TCA cycle

A

M2 like

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13
Q

neutrophils normally are purely glycolytic to support ___and __-

A

ATP generation and microbial killing

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14
Q

neutrophils in cancer it is considered glucose restricted conditions, neutrophils engage in oxidative mitochondrial metabolism and fatty acid oxidation to support NADPH oxidase dependent ___

A

ROS production

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15
Q

the increase in glycolytic activity of cancer cells combined with poor vascular exchange results in: ____

A

-decrease glucose in TME
-limit in T cell expansion
-decrease in effector function through competition or altered apoptosis or eventual exhaustion

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16
Q

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

A

low glucose, acidity or lactate

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17
Q

antibodies against immune checkpoint bloackade receptors restores?

A

glycolysis

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18
Q

most promising therapy: immune checkpoint blockade (ICB) restores ____ metabolism and effector function in TILs

A

anabolic

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19
Q

accumulation of lactate in TME promote immunosuppressive immune cells through m2 macrophage polarization, MDSC infiltration, Treg survival and inhibiting T effector functions
-decreasing lactate: by inhibiting ___or neutralizing ____
-checkpoint receptor VISTA: using ___exploits TME to imrpove treatment specificity. targeting this can be TME-context and immune cell specific so anticancer effects still unclear

A
  1. lactate producing enzyme LDH, inhibiting lactate transporters MCT1/4 or neutralizing lactic acid induced acidity
  2. acidic PH selective antibody
20
Q

increase in glycolytic activity of cancer cells under hypoxic condition ____which acidifies TME

A

increase lactate build up

21
Q

____: LDH is correlated with tumor size and clinical severity

A

LDH

22
Q

lactic acid inhibit effector T cell function through decrease proliferation by inhibiting monocyte activation and dendritic cell differentiation it promotes m2 polarization through ____
-lactic acid can also boost Treg survival in TME, due to Tregs ability to oxidize exogenous lactate

A

increase arginase and HIF-1alpha stabilization

23
Q

___: inhibits natural killer cells function and increase MDSCs contributing to suppressive microenviornment

A

lactate

24
Q

___: relieas on nitric oxide synthetase (NOS) and arginase (ARG) enzyme

A

arginine metabolism

25
Q

what role does tryptophan play in TME? cancer cells alter the chemical composition of the extracellular milieu, this exerts ____on the phenotypes of normal cells in the tumor extracellular matrix
-the microenvironment affects metabolism and signaling responses of cancer cells

A

pleiotropic effects

26
Q

glutamine metabolism is altered as a result of TME inhibiting glutaminolysis through blocking ____, this promotes a pro-inflammatory macrophage phenotype

A

glutaminase (GLS)

27
Q

therapies that facilitate metabolism of arginine through iNOS cor cancer therapy; macrophages using iNOS have ___phenotype. their NO secretion promotes T cell extravasion and homing against tumors
-macrophage derived NO results in ___which is important for T cell extravastation

A

1.M1 like
2. decrease VCAM-1

28
Q

tregs, tolergenic DCs and MDSCs have increased expresion of ___

A

indoleamine 2,3 dioxygenase (IDO)

29
Q

why is IDO important?

A

its the enzyme responsible for metabolizing tryptophan to kynurenine

30
Q

targeting IDO suppress the immune subsets reducing ___in the microenviornment

A

kynurenine

31
Q

T cell infiltration into tumor from blood involves?
-through these t cell is able to go through cell junctions of blood vessels into tissue along chemokines making vascular cell adhesion molecule (VCAM-1)

A
  1. selectins and their ligands
  2. chemokines and their receptors
  3. integrins and their ligands
32
Q

hypoxia mediated events limit the energy supply by reducing ___lvels in TME with ___. this occurs by breakdown of ATP by ectonucleotidases CD39 and CD37

A

decrease ATP, increase of adenosine

33
Q

___: hydrolyzes ATP to ADP and AMP

A

CD39

34
Q

____: catabolize extracellular AMP, converting it to adenosine

A

CD73

35
Q

engagement of extracellular adenosine and A2AR receptors on surface of T cells, NK cells, macrophages/dendritic cells and neutrophils leads to long lasting tumor growth makes good target for cancer therapy
-blockade of ___: maintain ATP in TME by preventing its degradation
-Blockade of ___: block adenosine generation
-Blockade of ____: block the activity of adenosine

A
  1. blockade CD39
  2. Blockade of CD73
  3. Blockade of A2AR
36
Q

____; is essential for T cell proliferation, serving as a precursor for protein and lipid biosynthesis

A

glutamine

37
Q

____: glutamine enters through several plasma membrane glutamine transporter and is used in the cytosol in biosynthesis of nucleotides, asparagnine and UDP-GLcNAC

A

glutamine metabolic pathways

38
Q

glutamine derived alpha ketoglutarate supplies metabolite for TCA cycle and fuels the generation of 2-HG under conditions of ____or ____

A

IDH2 mutation or hypoxia

39
Q

_____via reductive carboxylation supports fatty acid synthesis under hypoxia or HIF-2a transcription factor stabilization

A

citrate derived from glutamine

40
Q

glutamine is catabolized into glutamate by glutaminase (GLS) then internalized into mitochondria and converted to alpha ketogluterate and then entering/fueling TCA cycle
-alternate pathway for fatty acid synthesis is reductive carboxylation which involves carbon produced by glutamine metabolism; glutamine derived alpha ketoglutarate is reduced by the consumption of ___ in the reverse reaction to form citrate

A

NaDPH by isocitrate dehydrogenase (IDH)

41
Q

glutamine has an essential role in ATP production, de novo synthesis of nucleotides (DNA and RNA) and production of macromolecules; glutaminase potential target for cancer therapy (glutaminase inhibitors) for _____

A

solid tumors

42
Q

___: is a mitochondrial enzyme that catalyzes oxidative decarboxylation of isocitrate to alphaketoglutarate

A

IDH2

43
Q

____: conversion of alpha ketogluterate to D-2 hydroxyglutarate (2HG); result in excess 2HG a competitive inhibitor needed for demethylation of cytosine nucleotides in DNA

A

IDH2 mutations

44
Q

increase fatty acids in TME result in ___in immune cells or promote FAO
-immune suppressive phenotypes rely on FAO to produce energy

A

increase lipid droplets

45
Q

targeting ___ or ___ is an area for cancer therapy

A

FASN or ACC

46
Q

____: is a facilitator of FA transport in tissues with a high capacity for fatty acid metabolism

A

CD36

Health Studies (8 decks)

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