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Timing of the Major Metabolic Switches in Immune Cell Activation and Differentiation During Cancer Development

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Immuno-Oncology Crosstalk and Metabolism

Abstract

The immune system is divided into two parts: innate and adaptive. Immune cells derived from myeloid and lymphoid progenitor cells play a critical role in combating infection, cell stress, cancer, and autoimmune responses by mounting appropriate and robust immune responses. According to the evidence, an immune cell’s nutrient uptake and utilization are critical for governing their proliferation and differentiation and influencing metabolic pathways that lead to immune cell fate. Cancer development is characterized by altered metabolism. Metabolism and immune system are inextricably linked, and multi level interactions between them shape immune responses. This chapter deliberates potential metabolic switches in immune cells which modulate the activation, differentiation, and response to fight against a tumor. We believe that it is possible to design new treatments for cancer therapy to steer a specific immune cell metabolism.

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Abbreviations

A2b:

Adenosine receptor

ACC1:

Acetyl coenzyme A carboxylase

AKT:

AKT serine threonine kinase

AMP:

Adenosine monophosphate

AMPK:

5′-Activated protein kinase

APCs:

Antigen-presenting cells

Arg-1:

Arginase-1

COX10:

Cytochrome C oxidase assembly factor heme A:farnesyltransferase COX10

COX2:

Cyclooxygenase 2

CTLs:

Cytotoxic T lymphocytes

DAMP:

Damage-associated molecular pattern

DCs:

Dendritic cells

ERK:

Extracellular signal-regulated kinases

ETC:

Electron transport chain

FADH2:

Flavin adenine dinucleotide 2

FAO:

Fatty acid oxidation

FOXP3:

Forkhead box P3

G6P:

Glucose-6-phosphate

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GCN2:

General control nonderepressible 2

GLUT1:

Glucose transporter 1

HIF1α:

Hypoxia-inducible factor 1

IC:

Immune complexes

IDO:

Indoleamine 2,3-dioxygenase

IFN-γ:

Interferon gamma

IL-1:

Interleukin-1

IL-10:

Interleukin-10

IL-12:

Interleukin-12

IL-13:

Interleukin-13

IL-17:

Interleukin-17

IL-4:

Interleukin-4

IL-6:

Interleukin-6

IL-7:

Interleukin-7

iNOS:

Inducible nitric oxide synthase

JAK:

Janus kinase

LDHA:

Lactate dehydrogenase A

LPS:

Liposaccharide

M1/M2:

Macrophages

MDSCs:

Myeloid-derived suppressor cells

MHC-I/-II:

Major histocompatibility complex I/II

MMPs:

Metalloproteases

mROS:

Mitochondrial reactive oxygen species

MSR1:

Macrophage scavenger receptor 1

mTOR:

Mammalian target of rapamycin

mTORC1:

mTOR complex 1

mTORC2:

mTOR complex 2

MΦs:

Macrophages

NADH:

Nicotinamide adenine dinucleotide

NETs:

Neutrophil extracellular traps

NFAT:

Nuclear factor of activated T cells

NF-κB:

Nuclear factor kappa B

NK:

Natural killer

NOS2:

Nitric oxide synthase 2

OXPHOS:

Oxidative phosphorylation

PAMPs:

Pathogen-associated molecular pattern

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed death-ligand 1

PDPK1:

Phosphoinositide-dependent protein

PEP:

Phosphoenolpyruvate

PEPCK1:

Phosphoenolpyruvate carboxykinase 1

PGC-1β:

Proliferator-activated receptor-γ coactivator-1 beta

PI3K:

Phosphoinositide 3-kinase

PKM2:

Pyruvate kinase M1/2

PPAR-γ:

Peroxisome proliferator-activated receptor gamma

PPP:

Pentose phosphate shunt/pathway

PTEN:

Phosphatase and tensin homolog

RNS:

Reactive nitrogen species

RORγ:

RAR-related orphan receptor gamma

ROS:

Reactive oxygen species

S-2HG:

S-2-hydroxyglutarate

SHTM2:

Serine hydroxymethyltransferase 2

SIRT:

Sirtuin

SREBP:

Sterol regulatory element-binding protein

STAT:

Signal transducer and activator of transcription

STAT6:

Signal transducer and activator of transcription 6

TADCs:

CCR7, tumor-associated DCs

TAG:

Triacylglycerol

TAMs:

Tumor-associated macrophages

TANs:

Tumor-associated neutrophils

TCA:

Tricarboxylic acid

TCR:

T-cell receptor

TGF-β:

Transforming growth factor beta

TME:

Tumor microenvironment

TNFα:

Tumor necrosis factor alpha

Tregs:

T regulatory cells

TSC-1:

Tuberous sclerosis 1

VEGF:

Vascular endothelial growth factor

VHL:

Von Hippel-Lindau

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Acknowledgments

Figure prepared by using Biorender and AI.

Author Contributions

R.S. conceived and authored the chapter’s first draft and provided little information. The chapter was critically reviewed, and an abbreviation list was created by A.V. and C.R. Most numbers of figures were supplied by U.A. All authors read and approved the final draft of the chapter.

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA

    Sanjay Rathod

  2. Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA

    Vaishali Aggarwal

  3. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Arun Upadhyay

  4. Center of Emphasis in Cancer, Paul L. Foster School of Medicine, Department of Molecular and Translation Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA

    Ramesh Choudhari

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  1. Sanjay Rathod
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  4. Ramesh Choudhari
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Correspondence to Sanjay Rathod .

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Editors and Affiliations

  1. Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Jammu and Kashmir, India

    Muzafar Ahmad Macha

  2. Molecular and Metabolic Imaging Laboratory, Sidra Medicine, Doha, Qatar

    Ajaz Ahmad Bhat

  3. Department of Biotechnology, Central University of Kashmir, Ganderbal, Jammu and Kashmir, India

    Nissar Ahmad Wani

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Rathod, S., Aggarwal, V., Upadhyay, A., Choudhari, R. (2022). Timing of the Major Metabolic Switches in Immune Cell Activation and Differentiation During Cancer Development. In: Macha, M.A., Bhat, A.A., Wani, N.A. (eds) Immuno-Oncology Crosstalk and Metabolism. Springer, Singapore. https://doi.org/10.1007/978-981-16-6226-3_7

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