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γδ T 细胞是儿童神经母细胞瘤中主要的抗肿瘤 T 细胞

英文原题:γδ T cells are the prime antitumoral T cells in pediatric neuroblastoma.

PubMed 2025/09/02(内容时间) Life Sci Alliance Q2 · IF 3.1(JCR 2025)

研究概要

这一发现为神经母细胞瘤患者的免疫治疗创造了机会窗口,T 细胞可能是潜在的初始应答者。

中文摘要

尽管接受强化治疗,高危儿童神经母细胞瘤患者的生存率仍极低,因此亟需新的治疗选择。虽然神经母细胞瘤HLA表达低且免疫细胞浸润有限,但出现TIL(肿瘤浸润淋巴细胞)提示患者生存较好。在此,我们发现诱导化疗后多数肿瘤病灶仍含有存活的免疫细胞浸润,且CD3+ T细胞比例较高。因此我们扩增了TIL,并检测其抗肿瘤活性。只要起始细胞材料充足,其扩增效率可达到与成人实体瘤相当的水平。然而,成人肿瘤来源的TIL产品几乎全部由T细胞构成,而神经母细胞瘤来源的TIL产品中,T细胞和T细胞均可有效扩增。重要的是,针对自体肿瘤消化物的抗肿瘤应答主要来自(表达Vγ1和Vγ3的)T细胞,而非T细胞。总之,这一发现为神经母细胞瘤患者开展免疫治疗创造了机会,T细胞有望成为主要效应细胞。

展开英文摘要原文

High-risk pediatric neuroblastoma patients have a dismal survival rate despite intensive treatment regimens. New treatment options are thus required. Even though HLA expression in neuroblastoma is low and immune cell infiltrates are limited, the presence of tumor-infiltrating lymphocytes (TILs) is indicative of better patient survival. Here, we show that most tumor lesions contain viable immune cell infiltrates after induction chemotherapy, with high percentages of CD3 + T cells. We therefore expanded the TILs and tested their antitumoral activity. With sufficient starting material, TIL expansion was as efficient as for adult solid tumors. However, whereas TIL products from adult tumors almost exclusively contained T cells, in neuroblastoma-derived TIL products, T cells expanded with similar efficacy as T cells. Importantly, the antitumor responses in response to autologous tumor digest primarily originated from (V 1- and V 3-expressing) T cells, and not from T cells. In conclusion, this finding creates a window of opportunity for immunotherapy for neuroblastoma patients, with T cells as potential prime responders.

论文信息

作者
Castenmiller SM、Borst AL、Wardak L、Molenaar JJ、Papadopoulou M、de Krijger RR、van der Steeg AF、van Noesel MM
第一作者单位
Sanquin Blood Supply Foundation, Department of Research, T Cell Differentiation Lab, Amsterdam, The Netherlands.Netherlands
通讯作者单位
Sanquin Blood Supply Foundation, Department of Research, T Cell Differentiation Lab, Amsterdam, The Netherlands m.wolkers@sanquin.nl.Netherlands
文献类型
非美国政府资助研究
期刊
Life science alliance2025 Nov
原文标识
PubMed 40897471 · DOI 10.26508/lsa.202503249