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母体免疫会损害后代淋巴瘤的生长以及中枢神经系统/眼部转移。

Maternal immunization impairs lymphoma growth and CNS/ocular metastasis in the offspring.

作者信息

Braitbard Ori, Bar-Sinai Allan, Hochman Jacob

机构信息

Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem, Israel.

Department of Bioinformatics, The Faculty of Life and Health Sciences, Jerusalem College of Technology, Jerusalem, Israel.

出版信息

Front Immunol. 2024 Dec 18;15:1498272. doi: 10.3389/fimmu.2024.1498272. eCollection 2024.

Abstract

Maternal immunization is an important tool directed against a variety of infectious maladies in the offspring. A complementary, but less explored area is the use of maternal immunization in the prevention and treatment of childhood cancers. This in part stems from the lack of adequate experimental model systems. Lymphomas of the Central Nervous System (CNS) and ocular involvement pose a therapeutic challenge. Ocular lymphoma is a lethal disease caused mainly by two clinically distinct forms of non-Hodgkin's lymphoma: non-Hodgkin's lymphoma of the central nervous system, or Primary CNS lymphoma (PCNSL), and systemic lymphoma metastatic to the eye. Previously, we developed an experimental model whereby mouse lymphoma cell variants, derived from the S49 T-cell lymphoma, metastasized to the CNS and eyes following Intraperitoneal inoculation at days 7-10 postnatal. Here, we extended the model to study whether maternal immunization can impede CNS/Ocular metastasis in the offspring exposed to the metastatic lymphoma cells. To that effect, female Balb/C mice were vaccinated with either immunogenic, live, S49 lymphoma cell variants, or with a purified protein antigen: the 98 amino acid signal peptide of the envelop precursor protein of Mouse Mammary Tumor Virus (MMTV) endogenously harbored by the S49 lymphoma. The offspring from both vaccination protocols were immunized against a challenge with the CNS/Ocular metastatic lymphoma cells. Immunity was conferred via milk suckling and was prolonged without further challenge for an extended period of at least 3 months. The abovementioned findings constitute a novel experimental model system whereby CNS/Ocular metastasis of malignant lymphoma in the offspring is impeded through maternal vaccination/immunization and thus, can be followed mechanistically as well as for novel therapeutic modalities.

摘要

母体免疫是预防后代多种传染病的重要手段。一个与之互补但较少被探索的领域是利用母体免疫来预防和治疗儿童癌症。这在一定程度上源于缺乏足够的实验模型系统。中枢神经系统(CNS)淋巴瘤和眼部受累带来了治疗挑战。眼部淋巴瘤是一种致命疾病,主要由两种临床上不同形式的非霍奇金淋巴瘤引起:中枢神经系统非霍奇金淋巴瘤,即原发性中枢神经系统淋巴瘤(PCNSL),以及转移至眼部的系统性淋巴瘤。此前,我们开发了一种实验模型,通过该模型,源自S49 T细胞淋巴瘤的小鼠淋巴瘤细胞变体在出生后第7 - 10天腹腔接种后转移至中枢神经系统和眼睛。在此,我们扩展了该模型,以研究母体免疫是否能阻止暴露于转移性淋巴瘤细胞的后代发生中枢神经系统/眼部转移。为此,雌性Balb/C小鼠接种具有免疫原性的活S49淋巴瘤细胞变体,或接种纯化的蛋白抗原:S49淋巴瘤内源性携带的小鼠乳腺肿瘤病毒(MMTV)包膜前体蛋白的98个氨基酸信号肽。两种接种方案的后代均针对中枢神经系统/眼部转移性淋巴瘤细胞的攻击进行免疫。免疫通过哺乳获得,并在至少3个月的延长时间内无需进一步攻击而持续。上述发现构成了一种新的实验模型系统,通过母体接种/免疫可阻止后代恶性淋巴瘤的中枢神经系统/眼部转移,因此,可以从机制上以及新的治疗方式方面进行跟踪研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0d9/11688474/7571345dd6c1/fimmu-15-1498272-g001.jpg

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