PuSH - Publikationsserver des Helmholtz Zentrums München

Vaupel, P.* ; Multhoff, G.

Adenosine can thwart antitumor immune responses elicited by radiotherapy : Therapeutic strategies alleviating protumor ADO activities.

Strahlenther. Onkol. 192, 279-287 (2016)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
BACKGROUND: By studying the bioenergetic status we could show that the development of tumor hypoxia is accompanied, apart from myriad other biologically relevant effects, by a substantial accumulation of adenosine (ADO). ADO has been shown to act as a strong immunosuppressive agent in tumors by modulating the innate and adaptive immune system. In contrast to ADO, standard radiotherapy (RT) can either stimulate or abrogate antitumor immune responses. Herein, we present ADO-mediated mechanisms that may thwart antitumor immune responses elicited by RT. MATERIALS AND METHODS: An overview of the generation, accumulation, and ADO-related multifaceted inhibition of immune functions, contrasted with the antitumor immune effects of RT, is provided. RESULTS: Upon hypoxic stress, cancer cells release ATP into the extracellular space where nucleotides are converted into ADO by hypoxia-sensitive, membrane-bound ectoenzymes (CD39/CD73). ADO actions are mediated upon binding to surface receptors, mainly A2A receptors on tumor and immune cells. Receptor activation leads to a broad spectrum of strong immunosuppressive properties facilitating tumor escape from immune control. Mechanisms include (1) impaired activity of CD4 (+) T and CD8 (+) T, NK cells and dendritic cells (DC), decreased production of immuno-stimulatory lymphokines, and (2) activation of Treg cells, expansion of MDSCs, promotion of M2 macrophages, and increased activity of major immunosuppressive cytokines. In addition, ADO can directly stimulate tumor proliferation and angiogenesis. CONCLUSION: ADO mechanisms described can thwart antitumor immune responses elicited by RT. Therapeutic strategies alleviating tumor-promoting activities of ADO include respiratory hyperoxia or mild hyperthermia, inhibition of CD39/CD73 ectoenzymes or blockade of A2A receptors, and inhibition of ATP-release channels or ADO transporters.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
2.898
0.922
29
30
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Adenosine ; Immunostimulation ; Immunosuppression ; Radiotherapy ; Tumor Hypoxia ; Tumor Progression; Regulatory T-cells; Tumor Progression; Ionizing-radiation; Solid Tumors; Cancer; Hypoxia; Inflammation; Accumulation; Protection; Receptors
Sprache
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 0179-7158
e-ISSN 1439-099X
Quellenangaben Band: 192, Heft: 5, Seiten: 279-287 Artikelnummer: , Supplement: ,
Verlag Urban & Vogel
Verlagsort Munich
Begutachtungsstatus Peer reviewed
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Radiation Sciences
PSP-Element(e) G-501300-001
Scopus ID 84960154143
PubMed ID 26961686
Erfassungsdatum 2016-03-18