{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:19:52Z","timestamp":1793762392005,"version":"4.6.1"},"reference-count":78,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"648","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,6,8]]},"abstract":"<jats:p>Tumor evasion of immune destruction is associated with the production of immunosuppressive adenosine in the tumor microenvironment (TME). Anticancer therapies can trigger adenosine triphosphate (ATP) release from tumor cells, causing rapid formation of adenosine by the ectonucleotidases CD39 and CD73, thereafter exacerbating immunosuppression in the TME. The goal of this study was to develop an approach to facilitate cancer therapy\u2013induced immunogenic cell death including ATP release and to limit ATP degradation into adenosine, in order to achieve durable antitumor immune response. Our approach was to construct reactive oxygen species (ROS)\u2013producing nanoparticles that carry an ectonucleotidase inhibitor ARL67156 by electronic interaction and phenylboronic ester. Upon near-infrared irradiation, nanoparticle-produced ROS induced ATP release from MOC1 cancer cells in vitro and triggered the cleavage of phenylboronic ester, facilitating the release of ARL67156 from the nanoparticles. ARL67156 prevented conversion of ATP to adenosine and enhanced anticancer immunity in an MOC1-based coculture model. We tested this approach in mouse tumor models. Nanoparticle-based ROS-responsive drug delivery reprogramed the immunogenic landscape in tumors, eliciting tumor-specific T cell responses and tumor regression, conferring long-term survival in mouse models. We demonstrated that TME reprograming sets the stage for response to anti-programmed cell death protein 1 (PD1) immunotherapy, and the combination resulted in tumor regression in a 4T1 breast cancer mouse model that was resistant to PD1 blockade. Furthermore, our approach also induced immunological effects in patient-derived organotypic tumor spheroid model, suggesting potential translation of our nanoparticle approach for treating human cancers.<\/jats:p>","DOI":"10.1126\/scitranslmed.abh1261","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T17:56:36Z","timestamp":1654710996000},"source":"Crossref","is-referenced-by-count":116,"title":["Delivery of an ectonucleotidase inhibitor with ROS-responsive nanoparticles overcomes adenosine-mediated cancer immunosuppression"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3250-7733","authenticated-orcid":true,"given":"Chengqiong","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9124-3531","authenticated-orcid":true,"given":"Stacy","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Porosnicu","sequence":"additional","affiliation":[{"name":"Depatment of Internal Medicine - Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA."},{"name":"Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9022-2229","authenticated-orcid":true,"given":"Alexandra","family":"Thomas","sequence":"additional","affiliation":[{"name":"Depatment of Internal Medicine - Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA."},{"name":"Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-7961","authenticated-orcid":true,"given":"Gregory L.","family":"Kucera","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA."},{"name":"Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos I.","family":"Votanopoulos","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA."},{"name":"Department of Surgery - Section of Surgical Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5220-3887","authenticated-orcid":true,"given":"Shaomin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; 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