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We screened for genes targeted by tazemetostat in eleven B\u2010cell lymphoma cell lines and found that tazemetostat significantly increased the expression of chemokine (C\u2010C motif) ligand 17 (<jats:italic>CCL17<\/jats:italic>)\/thymus\u2010 and activation\u2010regulated chemokine (<jats:italic>TARC<\/jats:italic>) in all, which codes for a chemokine that is a hallmark of Hodgkin\/Reed\u2010Sternberg (H\/RS) cells in Hodgkin lymphoma. Notably, gene set enrichment analysis demonstrated a positive correlation between the genes upregulated by tazemetostat in five follicular lymphoma (FL) cell lines and those reported to be overexpressed in H\/RS cells. The <jats:italic>CCL17<\/jats:italic> promoter region was enriched in repressive histone modification H3K27me3, and tazemetostat induced H3K27 demethylation and activated gene transcription. CCL17 protein secretion was also induced by EZH2 inhibition, which was further enhanced by concurrent CpG stimulation. In vitro transwell migration assay demonstrated that CCL17 produced by tazemetostat\u2010treated B cells enhanced the recruitment of T cells, which had the potential to exert antilymphoma response. Analysis of publicly available human lymphoma databases showed that <jats:italic>CCL17<\/jats:italic> gene expression was inversely correlated with the EZH2 activation signature and significantly paralleled the CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cell\u2013rich signature in FL and germinal center B\u2010cell\u2013like diffuse large B\u2010cell lymphoma. Our findings indicate that tazemetostat can potentially activate antilymphoma response by upregulating <jats:italic>CCL17<\/jats:italic> expression in B\u2010cell lymphoma cells and promote T\u2010cell recruitment, which provides a rationale for its combination with immunotherapy.<\/jats:p>","DOI":"10.1111\/cas.15122","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T18:25:01Z","timestamp":1630088701000},"page":"4604-4616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The EZH2 inhibitor tazemetostat upregulates the expression of CCL17\/TARC in B\u2010cell lymphoma and enhances T\u2010cell recruitment"],"prefix":"10.1111","volume":"112","author":[{"given":"Hepei","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology Graduate School of Medicine Kyoto University Kyoto 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