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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Immunoregulatory and Effector Activities of Nitric Oxide and Reactive Nitrogen Species in Cancer

Author(s): Cinzia Fionda, Maria Pia Abruzzese, Angela Santoni and Marco Cippitelli

Volume 23 , Issue 24 , 2016

Page: [2618 - 2636] Pages: 19

DOI: 10.2174/0929867323666160727105101

Price: $65


Nitric Oxide (NO) is a signaling radical, highly diffusible pleiotropic regulator of a large set of different molecular and biological pathways, including, neurotransmission, vasodilatation and macrophagemediated responses against infections. It is produced from the amino acid L-Arginine and oxygen by the enzymatic action of three isoforms of the Nitric Oxide Synthase (NOS), differently expressed and regulated in tissues.

Increasing evidence highlights the wide spectrum of action of NO in different pathologic conditions, including cancer. In this regard, a dual role for this molecule as a pro- and anti-tumorigenic mediator has been described, in a context and concentration-dependent manner. Moreover, NO exerts numerous immunologic effects, by operating as an effector molecule in innate immune responses as well as a regulator of adaptive immune components.

Here, we will review recent advances in the field of biology of this pleiotropic signaling molecule in cancer, also providing a concise description of the immunoregulatory and effector activities of NO and Reactive Nitrogen Species (RNS). In particular, we will summarize recent knowledge of the molecular mechanisms underlying the complex functions of NO in cancer pathogenesis. We will also address emerging immune-mediated mechanisms regulated by NO to provide a comprehensive view of the complex cellular interactions which control cancer progression and that can be influenced by NO at multiple levels. In the light of different immunologic effects of this molecule, the potential therapeutic implications of novel drugs targeting NO to treat cancer and to improve anti-tumor immune responses will be discussed.

Keywords: Nitric Oxide, RNS, Cancer, Immune Escape, TAM, MDSCs, Nitric Oxide Donors, Microenvironment, Chemoimmunotherapy.

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