{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:04:00Z","timestamp":1788919440022,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50CA97274"],"award-info":[{"award-number":["P50CA97274"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA195568"],"award-info":[{"award-number":["U01 CA195568"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016866","name":"Henry J. Predolin Foundation for Research in Leukemia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Soluble tumor necrosis factor receptor 2 (sTNFR2) is a member of the TNF superfamily whose normal bodily distribution is largely limited to low level expression on lymphoid cells. It has emerged as an important inducible receptor that activates a signaling pathway for cancer growth. We evaluated sTNFR2 as a prognostic biomarker for overall survival (OS) in newly diagnosed lymphoma using a prospective cohort study with banked pretreatment serum samples. sTNFR2 was higher in 1513 lymphoma patients compared to 499 age and sex matched controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Using Kaplan\u2013Meier curves and Cox proportional hazards models to estimate hazard ratios [HR] (high vs. low tertile), higher levels of sTNFR2 at diagnosis were associated with inferior OS across all seven major lymphoma subtypes: Hodgkin lymphoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001; HR\u2009=\u200912.6), diffuse large B\u2010cell lymphoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001; HR\u2009=\u20092.6), follicular lymphoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.00017; HR\u2009=\u20092.5), mantle cell lymphoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001; HR\u2009=\u20094.2), small lymphocytic lymphoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.012; HR\u2009=\u20092.4), marginal zone lymphoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0012; HR\u2009=\u20093.1), and T\u2010cell lymphoma (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001; HR\u2009=\u20093.1). Using CITE\u2010seq profiling of tumor microenvironment tissue, we sought to identify cellular source(s) of circulating sTNFR2. In tumor tissue from follicular lymphoma, high TNFR2\u2010expressing cells were found to be T\u2010regulatory (Treg) cells, suggestive of a Treg\u2010driven cancer. In tissue from a case of marginal zone lymphoma, high TNFR2 expression was found on CD4+ and CD8+ T cells, B cells, and monocytes but also directly on tumor cells. We conclude sTNRF2 is a strong prognostic biomarker of OS across major lymphoma subtypes and may be useful to guide therapeutic choices, including targeted therapies against immunosuppressive TNFR2\u2010expressing Tregs.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70293","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T10:33:46Z","timestamp":1774607626000},"page":"1388-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High Soluble Tumor Necrosis Factor Receptor 2 in Serum Is Associated With Inferior Overall Survival Across Major Lymphoma Subtypes"],"prefix":"10.1002","volume":"101","author":[{"given":"Arushi","family":"Khurana","sequence":"first","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Immunobiology Department General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany","family":"Thach","sequence":"additional","affiliation":[{"name":"Immunobiology Department General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Zhang","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna J.","family":"Negaard","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota 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M.","family":"Habermann","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-4712","authenticated-orcid":false,"given":"Susan L.","family":"Slager","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota 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