不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Fucosylation Promotes Cytolytic Function and Accumulation of NK Cells in B Cell Lymphoma.
Fucosylation Promotes Cytolytic Function and Accumulation of NK Cells in B Cell Lymphoma.
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研究已证实,自然杀伤(NK)细胞可产生强效抗肿瘤免疫应答,是有前景的细胞疗法。然而,NK细胞用于肿瘤免疫治疗,尤其治疗晚期血液系统和实体恶性肿瘤,仍受限于输注细胞体内存活能力下降、持留时间较短。本研究发现,NK细胞中岩藻糖基转移酶7和8(FUT7、FUT8)高表达;临床B细胞淋巴瘤发展过程中,CLA表达与NK细胞积累呈正相关。通过酶介导在体外进行细胞表面岩藻糖化,可显著增强NK细胞对B细胞淋巴瘤的杀伤作用。岩藻糖化还可通过增强NK细胞与E-选择素结合,促进其积聚于B细胞淋巴瘤靶组织。此外,NK细胞岩藻糖化也增强了T细胞抗肿瘤免疫应答。这些发现提示,体外岩藻糖化有助于增强NK细胞效应功能,可能成为肿瘤免疫治疗的新策略。
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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