{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:06:05Z","timestamp":1792739165737,"version":"4.5.0"},"reference-count":36,"publisher":"American Association for Cancer Research (AACR)","issue":"10","funder":[{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["R35CA19735301"],"award-info":[{"award-number":["R35CA19735301"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This multicenter phase I\/II clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. Twenty-nine enrolled patients received 4 Gy of radiation followed by 5 weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse events occurred. Nearly all patients had tumor reduction at their treated site. More importantly, 24 patients had tumor reduction at their nontreated sites, with 5 patients achieving a partial response and one achieving a complete response. Treatment-related increases of CD8+ and CD4+ effector T cells and decreases of T follicular helper and T regulatory cells (Treg) were observed in the tumor microenvironment. Low pretreatment levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells were associated with favorable outcomes. Intratumoral SD-101 in combination with low-dose radiation is well tolerated and results in regression of both treated and untreated sites of disease.<\/jats:p>\n                  <jats:p>Significance:\u2008In situ vaccination with the TLR9 agonist SD-101, along with low-dose radiation, was safe and induced systemic responses in patients with indolent lymphoma. Low levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells in the tumor microenvironment predicted favorable response to treatment. Cancer Discov; 8(10); 1258\u201369. \u00a92018 AACR.<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 1195<\/jats:p>","DOI":"10.1158\/2159-8290.cd-18-0743","type":"journal-article","created":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T03:26:05Z","timestamp":1535426765000},"page":"1258-1269","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":182,"title":["<i>In Situ<\/i>\n                    Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma"],"prefix":"10.1158","volume":"8","author":[{"given":"Matthew J.","family":"Frank","sequence":"first","affiliation":[{"name":"1Stanford University Hospital and Clinics, Division of Oncology, Stanford, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M.","family":"Reagan","sequence":"additional","affiliation":[{"name":"2University of Rochester Medical Center, Rochester, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"3Washington University School of Medicine, Siteman Cancer Center, St. Louis, Missouri."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-7064","authenticated-orcid":false,"given":"Leo I.","family":"Gordon","sequence":"additional","affiliation":[{"name":"4Feinberg School of Medicine, Northwestern University and the Robert H. 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