{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:09:37Z","timestamp":1772118577903,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Follicular lymphoma (FL) is characterized by an indolent clinical course and a high relapse rate, and often exhibits a diffuse pattern beyond the follicular area. Our group previously reported that immune checkpoint (ICP) pathways, such as programmed cell death (PD\u20101) and programmed death ligand 1 (PD\u2010L1), are poor prognostic factors for diffuse large B\u2010cell lymphoma and adult T\u2010cell leukemia\/lymphoma. In this study, the association between the expression of multiple ICP molecules according to immunohistochemistry and clinicopathological features in FL was determined via immunostaining of 173 biopsy samples. Membrane and\/or cytoplasm expression of CD86 (nCD86) and PD\u2010L1 (nPD\u2010L1) was found in tumor cells, whereas PD\u20101 (miPD\u20101), Galectin\u20109 (miGalectin\u20109), OX40 (miOX40), CTLA\u20104 (miCTLA\u20104), Tim\u20103 (miTim\u20103), OX40L (miOX40L), and LAG\u20103 (miLAG\u20103) were expressed in non\u2010neoplastic stromal cells. MiPD\u20101 expression was significantly higher in the follicular area than in the diffuse area (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0450). Expression of miOX40 and miCTLA\u20104 was significantly higher in the diffuse area than in the follicular area (respectively,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0053 and\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0092). MiTim\u20103 tended to be higher in the diffuse area than in the follicular area (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0616). MiTim\u20103 was significantly higher in relapse cases than in new\u2010onset cases (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0440); miLAG\u20103 tended to be higher in relapse cases than in new\u2010onset cases (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0622\n                    <jats:bold>,<\/jats:bold>\n                    not significant). The miOX40L\u2010high FL group had a significantly worse overall survival than the miOX40L\u2010low group (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0320). The expression of multiple ICP molecules on several cells reflects activated anti\u2010tumor immunity and the unique FL microenvironment. Further studies on gene expression or genomic abnormalities will reveal the clinical and biological significance of ICP molecules in FL.\n                  <\/jats:p>","DOI":"10.1002\/hon.2972","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T23:09:31Z","timestamp":1644016171000},"page":"530-540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinicopathological analysis of immunohistochemical expression of immune checkpoint molecules in follicular lymphoma"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-9755","authenticated-orcid":false,"given":"Eriko","family":"Yanagida","sequence":"first","affiliation":[{"name":"Department of Pathology Kurume University School of Medicine  Kurume, Fukuoka 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