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Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas

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Title: Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas
Authors: Chiba, Masahiro Browse this author
Shimono, Joji Browse this author
Ishio, Takashi Browse this author
Takei, Norio Browse this author
Kasahara, Kohei Browse this author
Ogasawara, Reiki Browse this author
Ara, Takahide Browse this author
Goto, Hideki Browse this author
Izumiyama, Koh Browse this author
Otsuguro, Satoko Browse this author
Perera, Liyanage P. Browse this author
Hasegawa, Hiroo Browse this author
Maeda, Michiyuki Browse this author
Hashino, Satoshi Browse this author
Maenaka, Katsumi Browse this author
Teshima, Takanori Browse this author
Waldmann, Thomas A. Browse this author
Yang, Yibin Browse this author
Nakagawa, Masao Browse this author →KAKEN DB
Issue Date: 2-Nov-2022
Publisher: American Society of Hematology
Journal Title: Blood
Volume: 140
Issue: 18
Start Page: 1951
End Page: 1963
Publisher DOI: 10.1182/blood.2022015646
Abstract: Adult T-cell leukemia/lymphoma (ATLL) is one of the aggressive peripheral T-cell neoplasms with a poor prognosis. Accumulating evidence demonstrates that escape from adaptive immunity is a hallmark of ATLL pathogenesis. However, the mechanisms by which ATLL cells evade natural killer (NK)-cell-mediated immunity have been poorly understood. Here we show that CD48 expression in ATLL cells determines the sensitivity for NK-cell-mediated cytotoxicity against ATLL cells. We performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening using 2 ATLL-derived cell lines and discovered CD48 as one of the best-enriched genes whose knockout conferred resistance to YT1-NK cell line-mediated cytotoxicity. The ability of CD48-knockout ATLL cells to evade NK-cell effector function was confirmed using human primary NK cells with reduced interferon-gamma (IFN gamma) induction and degranulation. We found that primary ATLL cells had reduced CD48 expression along with disease progression. Furthermore, other subgroups among aggressive peripheral T-cell lymphomas (PTCLs) also expressed lower concentrations of CD48 than normal T cells, suggesting that CD48 is a key molecule in malignant T-cell evasion of NK-cell surveillance. Thus, this study dem-onstrates that CD48 expression is likely critical for malignant T-cell lymphoma cell regulation of NK-cell-mediated immunity and provides a rationale for future evaluation of CD48 as a molecular biomarker in NK-cell-associated immunotherapies.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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