Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.904693
Keywords
fucosylation; NK cells; lymphoma; tumor immunotherapy; graft-versus-tumor effect
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Funding
- National Natural Science Foundation of China [81730003, 81700173, 81974001, 81900180, 82170222]
- National Science and Technology Major Project [2017ZX09304021]
- National Key R&D Program of China [2019YFC0840604, 2017YFA0104502]
- Key R&D Program of Jiangsu Province [BE2019798]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Jiangsu Medical Outstanding Talents Project [JCRCA2016002]
- Jiangsu Provincial Key Medical Center [YXZXA2016002]
- Jiangsu 333 Talent Project [BRA2015497]
- Jiangsu Social Development Program [BE2018651]
- Jiangsu Medical Junior Talent Person award [QNRC2016707]
- Applied Basic Research Programs of Suzhou City [SYS2018027]
- Suzhou Science and Technology Program Project [SLT201911]
- Jiangsu Natural Science Foundation [BK20211070]
- Key Disease Program of Suzhou [LCZX202101]
- China Postdoctoral Science Foundation [2019M661938]
- Jiangsu Planned Projects for Postdoctoral Research Funds [2019K098]
- Natural Science Foundation of Jiangsu Higher Education Institutions of China [20KJD320001]
- NIH [R35GM139643]
- Jiangsu Summit Six Top Talent Person project
- Translational Research Grant of NCRCH [2021ZKQC01]
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This study suggests that ex vivo fucosylation of NK cells enhances their effector functions in tumor immunotherapy. Fucosylation increases the cytolytic effect of NK cells against B cell lymphoma and promotes their accumulation in targeted tissues. Additionally, fucosylation also enhances T cell anti-tumor immune responses.
Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo. Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.
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