{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:58:06Z","timestamp":1791403086098,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010200","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RAPT Therapeutics"},{"DOI":"10.13039\/100001009","name":"Bristol-Myers Squibb Foundation","doi-asserted-by":"publisher","award":["1709-04-040"],"award-info":[{"award-number":["1709-04-040"]}],"id":[{"id":"10.13039\/100001009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV\n                    <jats:sup>+<\/jats:sup>\n                    tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (T\n                    <jats:sub>reg<\/jats:sub>\n                    ). Here, we show some EBV\n                    <jats:sup>+<\/jats:sup>\n                    tumor cells express high levels of the chemokines CCL17 and CCL22 both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    and that this expression mirrors the expression levels of expression of the EBV LMP1 gene\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Patient samples from lymphoblastic (Hodgkin lymphoma) and epithelial (nasopharyngeal carcinoma; NPC) EBV\n                    <jats:sup>+<\/jats:sup>\n                    tumors revealed CCL17 and CCL22 expression of both tumor cell-intrinsic and -extrinsic origin, depending on tumor type. NPCs grown as mouse xenografts likewise showed both mechanisms of chemokine production. Single cell RNA-sequencing revealed\n                    <jats:italic>in vivo<\/jats:italic>\n                    tumor cell-intrinsic CCL17 and CCL22 expression combined with expression from infiltrating classical resident and migratory dendritic cells in a CT26 colon cancer mouse tumor engineered to express LMP1. These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    T\n                    <jats:sub>reg<\/jats:sub>\n                    migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV\n                    <jats:sup>+<\/jats:sup>\n                    tumors.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010200","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T14:31:32Z","timestamp":1642084292000},"page":"e1010200","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["EBV+ tumors exploit tumor cell-intrinsic and -extrinsic mechanisms to produce regulatory T cell-recruiting chemokines CCL17 and CCL22"],"prefix":"10.1371","volume":"18","author":[{"given":"Aparna","family":"Jorapur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa 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X.","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1521-4557","authenticated-orcid":true,"given":"Omar","family":"Robles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-5279","authenticated-orcid":true,"given":"Jeffrey J.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9471-0043","authenticated-orcid":true,"given":"Valentin","family":"Baloche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1027-3400","authenticated-orcid":true,"given":"Pierre","family":"Busson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wustrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0105-1761","authenticated-orcid":true,"given":"Dirk G.","family":"Brockstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oezcan","family":"Talay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1471-1191","authenticated-orcid":true,"given":"Paul D.","family":"Kassner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-8904","authenticated-orcid":true,"given":"Gene","family":"Cutler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ppat.1010200.ref001","first-page":"1147","article-title":"Antibodies to Epstein-Barr virus in Burkitt\u2019s lymphoma and control groups","volume":"43","author":"G Henle","year":"1969","journal-title":"Journal of the National Cancer 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