{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:13:48Z","timestamp":1790784828375,"version":"4.1.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"2","license":[{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP160188"],"award-info":[{"award-number":["RP160188"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007313","name":"UT | University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["Seed funds from Center for Inflammation and Cancer"],"award-info":[{"award-number":["Seed funds from Center for Inflammation and Cancer"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["CA009598"],"award-info":[{"award-number":["CA009598"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["Summer program"],"award-info":[{"award-number":["Summer program"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,1,8]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Expression and regulation of IL-15 in the tumor microenvironment are poorly understood and are important as studies have provided correlative data that IL-15 expression within human tumors is a critical factor dictating antitumor responses. Moreover, IL-15 utilizes unique mechanisms that preclude typical expression analyses. Herein we demonstrate using multiple tumor models that soluble (s) IL-15\/IL-15R\u03b1 complexes are expressed in tumors and regulate tumor-infiltrating lymphocyte numbers. While the levels of sIL-15 complexes are low in established tumors, IL-15\u2013expressing myeloid cells are abundant. Nonetheless, providing a local inflammatory signal upregulates sIL-15 complexes within the tumor and drives tumor regression in an IL-15\u2013dependent manner. Thus, our findings reveal a strategy for unleashing a natural resource within tumors that enhances antitumor responses.<\/jats:p>","DOI":"10.1073\/pnas.1814642116","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T19:45:25Z","timestamp":1545853525000},"page":"599-608","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":131,"title":["IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7568-8167","authenticated-orcid":false,"given":"Rosa M.","family":"Santana Carrero","sequence":"first","affiliation":[{"name":"Immunology Graduate Program, University of Texas (UT) MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77584;"},{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Figen","family":"Beceren-Braun","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarai C.","family":"Rivas","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta M.","family":"Hegde","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achintyan","family":"Gangadharan","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Plote","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"},{"name":"Cancer Biology Graduate Program, University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77584"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Anthony","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of Texas (UT) MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77584;"},{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly S.","family":"Schluns","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of Texas (UT) MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77584;"},{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77584;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,12,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129139"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0b013e3182467d90"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3388"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2013.08.013"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307298101"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203479109"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444675"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007240"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121190"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00429-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705725200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2814"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-156307"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.017"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071913"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-384362"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120274"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600219"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.6072"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600240103"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900719"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307442101"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70036-7"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900420"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-277103"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12338641"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103609"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301389"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203149"},{"key":"e_1_3_3_30_2","first-page":"182","article-title":"Tumor-induced perturbations of cytokines and immune cell networks","volume":"1845","author":"Burkholder B","year":"2014","unstructured":"B Burkholder, , Tumor-induced perturbations of cytokines and immune cell networks. Biochim Biophys Acta 1845, 182\u2013201 (2014).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101159"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80564-6"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.05.029"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.019"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.017"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512832112"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.031"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301000"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80664-0"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81261"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301022110"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.59.4.476"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.54"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-3073"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5270.1947"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001601"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.5085"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062648"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008942828960"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00999-10"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.10.007"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8009221"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013693"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1814642116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1814642116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T03:37:32Z","timestamp":1649821052000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1814642116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,26]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,1,8]]}},"alternative-id":["10.1073\/pnas.1814642116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1814642116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,26]]},"assertion":[{"value":"2018-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}