{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:20:06Z","timestamp":1790274006607,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The tumor microenvironment regulates many aspects of cancer progression and anti-tumor immunity. Cancer cells employ a variety of immunosuppressive mechanisms to dampen immune cell function in the tumor microenvironment. While immunotherapies that target these mechanisms, such as immune checkpoint blockade, have had notable clinical success, resistance is common, and there is an urgent need to identify additional targets. Extracellular adenosine, a metabolite of ATP, is found at high levels in the tumor microenvironment and has potent immunosuppressive properties. Targeting members of the adenosine signaling pathway represents a promising immunotherapeutic modality that can potentially synergize with conventional anti-cancer treatment strategies. In this review, we discuss the role of adenosine in cancer, present preclinical and clinical data on the efficacy adenosine pathway inhibition, and discuss possible combinatorial approaches.<\/jats:p>","DOI":"10.3390\/ijms24108871","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T02:04:05Z","timestamp":1684289045000},"page":"8871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Targeting Immunosuppressive Adenosine Signaling: A Review of Potential Immunotherapy Combination Strategies"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-3391","authenticated-orcid":false,"given":"David","family":"Zahavi","sequence":"first","affiliation":[{"name":"Center for Immuno-Oncology (CIO), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm 8B13, 9000 Rockville Pike, Bethesda, MD 20879, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5282-3154","authenticated-orcid":false,"given":"James","family":"Hodge","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology (CIO), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm 8B13, 9000 Rockville Pike, Bethesda, MD 20879, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41568-021-00339-z","article-title":"Antigen presentation in cancer: Insights into tumour immunogenicity and immune evasion","volume":"21","author":"Jhunjhunwala","year":"2021","journal-title":"Nat. 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