| 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 |
| URI: | http://hdl.handle.net/2115/88935 |
| 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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