Adenosine Signaling in the Tumor Microenvironment
Adenosine, deriving from ATP released by dying cancer cells and then degradated in the tumor environment by CD39/CD73 enzyme axis, is linked to the generation of an immunosuppressed niche favoring the onset of neoplasia. Signals delivered by extracellular
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Adenosine Signaling in the Tumor Microenvironment Luca Antonioli, Matteo Fornai, Carolina Pellegrini, Vanessa D’Antongiovanni, Roberta Turiello, Silvana Morello, György Haskó, and Corrado Blandizzi
Abstract
Adenosine, deriving from ATP released by dying cancer cells and then degradated in the tumor environment by CD39/CD73 enzyme axis, is linked to the generation of an immunosuppressed niche favoring the onset of neoplasia. Signals delivered by extracellular
L. Antonioli (*) Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy e-mail: [email protected] M. Fornai · V. D’Antongiovanni · C. Blandizzi Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy C. Pellegrini Department of Pharmacy, University of Pisa, Pisa, Italy S. Morello Department of Pharmacy, University of Salerno, Fisciano, Italy R. Turiello Department of Pharmacy, University of Salerno, Fisciano, Italy PhD Program in Drug discovery and Development, Department of Pharmacy, University of Salerno, Fisciano, Italy G. Haskó Department of Anesthesiology, Columbia University, New York, NY, USA
adenosine are detected and transduced by G-protein-coupled cell surface receptors, classified into four subtypes: A1, A2A, A2B, and A3. A critical role of this nucleoside is emerging in the modulation of several immune and nonimmune cells defining the tumor microenvironment, providing novel insights about the development of novel therapeutic strategies aimed at undermining the immune-privileged sites where cancer cells grow and proliferate. Keywords
Adenosine · Adenosine receptors · Adenosine deaminase · Nucleoside transporters · CD73 · CD39 · Immune cells · Myeloid cells · Lymphocytes · Angiogenesis · Neoplasia · Tumor microenvironment · Metastasis · Apoptosis · Cell proliferation
9.1
Introduction
Until a few years ago, the term cancer defined an abnormal growth of cells which tend to proliferate in an uncontrolled way and, in some cases, to metastasize [1]. It has been for long conceived that hallmarks of cancer were intrinsic genetic features eliciting tumor development, proliferation, and progression and that targeting such cell
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021 A. Birbrair (ed.), Tumor Microenvironment, Advances in Experimental Medicine and Biology 1270, https://doi.org/10.1007/978-3-030-47189-7_9
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pathways could be sufficient to reach a therapeutic cancer control [1]. This simplistic view of the neoplastic disease has been radically changed since the introduction of the concept of tumor microenvironment (TME) [2]. Basically, the neoplastic microenvironment is a dynamic niche consisting of multiple cell types, including several immune cell populations (i.e., macrophages, neutrophils, mast cells, myeloidderived suppressor cells, dendritic cells, NK cells, T and B lymphocytes), cytokines, blood vessels, cancer cells, and their surroun
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