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Regulation of Anti-Tumor Immune Responses

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Nitric Oxide and Cancer: Pathogenesis and Therapy

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Abstract

Nitric oxide has a dual role in both regulation of immune homeostatsis and in responses to pathogens. It is therefore not surprising that a similar duality exists in the response against neoplastic cells. At the same time as NO can exert cytotoxicity against tumor cells it can also inhibit immune reactivity against these cells. The following chapter will recapitulate the basal roles of NO in immune homestasis and immune reactivity against pathogens followed by a more detailed review of the role of NO in immune reactivity against tumors. In experimental therapy against tumors, the positive effects of NO can thus be manipulated by administration of NO donors or by inducing NO secretion from innate immune cells. On the other hand, inhibition of NO release by NOS inhibitors or by inhibition of molecules upstream of NOS induction can boost adaptive immune responses mainly by T cells.

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Abbreviations

APC:

antigen presenting cell

CCL-2:

chemokine, also MCP-1 (monocyte chemotactic protein)

CNS:

central nervous system

COX:

cyclooxygenase

DC:

dendritic cell

eNOS:

endothelial nitric oxide synthase

FAS-L:

FAS-ligand; death receptor ligand

IFNγ:

Interferon gamma

GM-CSF:

granulocyte-macrphage colony stimulating factor

G-MDSC:

granulocytic-myeloid derived suppressor cells

HIF1α:

hypoxia inducible factor1-alfa

IL-1β:

interleukin-1beta

IL-2:

interleukin-2

IL-6:

interleukin-6

IL-10:

interleukin-10

IL-12:

interleukin-12

IL-18:

interleukin-18

IDO:

indoleamine 2, 3-dioxygenase

iNOS:

inducible endothelial nitric oxide synthase

LEC:

lymphatic endothelial cells

L-NAME:

L-NG-nitroarginine methyl ester

L-NIL:

N6- (1- iminoethyl)- L- lysine, dihydrochloride

L-NMMA:

N-Monomethyl-L-arginine, monoacetate

NSAID:

non steroidal anti-inflammatory drug

LPS:

lipopolysaccarhide

M1:

type 1 macrophage

MEG:

mercapto ethyl guandinidine

MDSC:

myeloid derived suppressor cells

Mo:

macrophage

Mo-MDSC:

monocytic-myeloid derived suppressor cells

MSC:

mesenchymal stromal cells

NF-κβ:

Nuclear factor kappa beta

NK:

natural killer

PD-L1:

programmed death receptor-1ligand; also B7-H1

PGE2 :

prostaglandin E2

ROS:

reactive oxygen species

RNS:

reactive nitrogen species

STAT3:

signal transducer and activator of transcription 3

TAA:

tumor associated antigens

TAM:

tumor associated macrophages

T cell:

T lymphocyte

TCR:

T cell receptor

TGFβ:

Transforming growth factor beta

Th1:

type 1 T helper lymphocyte

Th 17:

type 17 T helper lymphocyte

TNFα:

tumor necrosis factor-alpha

T reg:

regulatory T lymphocyte

TRAIL:

TNF-related apoptosis-inducing ligand

VEGF:

vascular endothelia l growth factor

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Acknowledgements

The author thanks Edward Visse for illustrations in Figs. 10.1 and 10.2.

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No potential conflicts of interest were disclosed

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  1. Section of Neurosurgery, Department of Clinical Sciences, Lund University, Lund, Sweden

    Peter Siesjö

  2. Department of Neurosurgery, Skane University Hospital, 22185, Lund, Sweden

    Peter Siesjö

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Correspondence to Peter Siesjö .

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  1. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California of Los Angeles, Los Angeles, California, USA

    Benjamin Bonavida

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Siesjö, P. (2015). Regulation of Anti-Tumor Immune Responses. In: Bonavida, B. (eds) Nitric Oxide and Cancer: Pathogenesis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-13611-0_10

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