{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:23:41Z","timestamp":1792023821326,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We previously examined the utility of rituximab\u2010bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R\u2010CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB\u2010treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. <jats:italic>CREBBP<\/jats:italic>, <jats:italic>KMT2D<\/jats:italic>, <jats:italic>MEF2B<\/jats:italic>, <jats:italic>BCL2<\/jats:italic>, <jats:italic>EZH2<\/jats:italic>, and <jats:italic>CARD11<\/jats:italic> were recurrently mutated as reported before, however none was predictive for progression\u2010free survival (PFS) in the RB\u2010treated patients (n\u00a0=\u00a034). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and\/or the immune response showed that expression levels of CD8<jats:sup>+<\/jats:sup> T\u2010cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24\u2010mo (POD24) group (n\u00a0=\u00a08) than in the no POD24 group (n\u00a0=\u00a031). Collectively, we selected 10 genes (<jats:italic>TBX21<\/jats:italic>, <jats:italic>CXCR3<\/jats:italic>, <jats:italic>CCR4<\/jats:italic>, <jats:italic>CD8A<\/jats:italic>, <jats:italic>CD8B<\/jats:italic>, <jats:italic>GZMM<\/jats:italic>, <jats:italic>FLT3LG<\/jats:italic>, <jats:italic>CD3E<\/jats:italic>, <jats:italic>EOMES<\/jats:italic>, <jats:italic>GZMK<\/jats:italic>), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB\u2010treated patients into immune IIS<jats:sup>high<\/jats:sup> (n\u00a0=\u00a019) and IIS<jats:sup>low<\/jats:sup> (n\u00a0=\u00a020) groups. The 3\u2010y PFS rate was significantly lower in the IIS<jats:sup>low<\/jats:sup> group than in the IIS<jats:sup>high<\/jats:sup> group (50.0% [95% CI: 27.1\u201069.2%] vs. 84.2% [95% CI: 58.7\u201094.6%], <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.460, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.00355). These results suggest that the T\u2010cell\u2010associated immune markers could be useful to predict prognosis in RB\u2010treated FL patients. (UMIN:000\u00a0013\u00a0795, jRCT:051\u00a0180\u00a0181)<\/jats:p>","DOI":"10.1111\/cas.15224","type":"journal-article","created":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T09:40:02Z","timestamp":1638006002000},"page":"660-673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Decreased expression of T\u2010cell\u2010associated immune markers predicts poor prognosis in patients with follicular lymphoma"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-9751","authenticated-orcid":false,"given":"Shinya","family":"Rai","sequence":"first","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-2720","authenticated-orcid":false,"given":"Kazuko","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Genome Biology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Hanamoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Faculty of Medicine Nara Hospital Kindai University Ikoma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-166X","authenticated-orcid":false,"given":"Mitsuhiro","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Hematology PL General Hospital Tondabayashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Hematology Minami Sakai Hospital Sakai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Haeno","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosaku","family":"Watatani","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kumode","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Serizawa","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0754-7415","authenticated-orcid":false,"given":"Yasuhiro","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikara","family":"Hirase","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-6666","authenticated-orcid":false,"given":"J. 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