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Immunol."],"abstract":"<jats:p>Antibody-dependent cellular phagocytosis (ADCP) by macrophages, an important effector function of tumor targeting antibodies, is hampered by \u2018Don\u00b4t Eat Me!\u2019 signals such as CD47 expressed by cancer cells. Yet, human leukocyte antigen (HLA) class I expression may also impair ADCP by engaging leukocyte immunoglobulin-like receptor subfamily B (LILRB) member 1 (LILRB1) or LILRB2. Analysis of different lymphoma cell lines revealed that the ratio of CD20 to HLA class I cell surface molecules determined the sensitivity to ADCP by the combination of rituximab and an Fc-silent variant of the CD47 antibody magrolimab (CD47-IgG\u03c3). To boost ADCP, Fc-silent antibodies against LILRB1 and LILRB2 were generated (LILRB1-IgG\u03c3 and LILRB2-IgG\u03c3, respectively). While LILRB2-IgG\u03c3 was not effective, LILRB1-IgG\u03c3 significantly enhanced ADCP of lymphoma cell lines when combined with both rituximab and CD47-IgG\u03c3. LILRB1-IgG\u03c3 promoted serial engulfment of lymphoma cells and potentiated ADCP by non-polarized M0 as well as polarized M1 and M2 macrophages, but required CD47 co-blockade and the presence of the CD20 antibody. Importantly, complementing rituximab and CD47-IgG\u03c3, LILRB1-IgG\u03c3 increased ADCP of chronic lymphocytic leukemia (CLL) or lymphoma cells isolated from patients. Thus, dual checkpoint blockade of CD47 and LILRB1 may be promising to improve antibody therapy of CLL and lymphomas through enhancing ADCP by macrophages.<\/jats:p>","DOI":"10.3389\/fimmu.2022.929339","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T01:56:52Z","timestamp":1666835812000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["Dual checkpoint blockade of CD47 and LILRB1 enhances CD20 antibody-dependent phagocytosis of lymphoma cells by macrophages"],"prefix":"10.3389","volume":"13","author":[{"given":"Tobias","family":"Zeller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Lutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira 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