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Venetoclax, a B\u2010cell lymphoma 2 (BCL\u20102) inhibitor for B\u2010cell malignancy, induces phosphatidylserine (PS) extracellular exposure, representing an \u201ceat\u2010me\u201d signal for macrophages. The present study aimed to explore whether TJC4\u2010Venetoclax combined therapy exerts synergistic anti\u2010cancer properties in B\u2010cell lymphoma. In vitro, flow cytometry and microscopy assessed whether TJC4 monotherapy or combination treatment could promote macrophage\u2010mediated phagocytosis of tumor cells. Induced PS exposure on the cell membrane was measured using flow cytometry with Annexin V\u2010FITC staining. In vivo, Venetoclax and TJC4's synergistic anti\u2010tumor effects were evaluated. B cell lymphoma cell lines express high levels of CD47 and patients with diffuse large B cell lymphoma expressing CD47 have a worse clinical prognosis. TJC4 eliminates tumor cells via macrophage\u2010mediated phagocytosis. In vitro and in vivo, the TJC4\u2010Venetoclax combination increased phagocytosis significantly compared with either agent alone, showing synergistic phagocytosis, and displayed synergistic anti\u2010cancer properties in B\u2010cell lymphoma. Our results support the TJC4\u2010Venetoclax combination as a promising therapy, and suppressing BCL\u20102 and CD47 simultaneously could represent a novel therapeutic paradigm for B\u2010cell lymphoma.<\/jats:p>","DOI":"10.1002\/hon.3009","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T18:59:06Z","timestamp":1651085946000},"page":"596-608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Anti\u2010CD47 immunotherapy in combination with BCL\u20102 inhibitor to enhance anti\u2010tumor activity in B\u2010cell lymphoma"],"prefix":"10.1002","volume":"40","author":[{"given":"Miaomiao","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Lymphoma Peking University Cancer Hospital &amp; 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Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dedao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Mi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyi","family":"Wang","sequence":"additional","affiliation":[{"name":"I\u2010Mab Biopharma  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ding","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Lymphoma Peking University Cancer Hospital &amp; 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