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辅酶 A 前体泛硫乙胺增强肉瘤的抗肿瘤免疫。

The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma.

机构信息

https://ror.org/03vyjkj45 INSERM, CNRS, Centre D'Immunologie de Marseille-Luminy, Aix-Marseille Université, Marseille, France

https://ror.org/03vyjkj45 INSERM, CNRS, Centre D'Immunologie de Marseille-Luminy, Aix-Marseille Université, Marseille, France.

出版信息

Life Sci Alliance. 2023 Oct 13;6(12). doi: 10.26508/lsa.202302200. Print 2023 Dec.

DOI:10.26508/lsa.202302200
PMID:37833072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10583838/
Abstract

The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell line that lacks Vnn1 expression, we showed that the administration of pantethine, a vitamin B5 precursor, attenuates tumor growth in immunocompetent but not nude mice. Pantethine boosts antitumor immunity, including the polarization of myeloid and dendritic cells towards enhanced IFNγ-driven antigen presentation pathways and improved the development of hypermetabolic effector CD8 T cells endowed with potential antitumor activity. At later stages of treatment, the effect of pantethine was limited by the development of immune cell exhaustion. Nevertheless, its activity was comparable with that of anti-PD1 treatment in sensitive tumors. In humans, expression correlates with improved survival and immune cell infiltration in soft-tissue sarcomas, but not in osteosarcomas. Pantethine could be a potential therapeutic immunoadjuvant for the development of antitumor immunity.

摘要

肿瘤微环境是一个由基质细胞、癌细胞和免疫细胞组成的动态网络，它们相互作用并争夺资源。我们之前已经确定 Vanin1 途径是通过维生素 B5 和辅酶 A 再生来抑制肉瘤发展的肿瘤抑制因子。使用一种缺乏 Vnn1 表达的侵袭性肉瘤细胞系，我们表明泛硫乙胺（维生素 B5 的前体）的给药可减弱免疫活性但非裸鼠中的肿瘤生长。泛硫乙胺可增强抗肿瘤免疫，包括髓样细胞和树突状细胞向增强 IFNγ 驱动的抗原呈递途径的极化，并改善具有潜在抗肿瘤活性的高代谢效应 CD8 T 细胞的发育。在治疗的后期阶段，泛硫乙胺的作用受到免疫细胞耗竭的发展的限制。尽管如此，其活性与敏感肿瘤中的抗 PD1 治疗相当。在人类中，表达与软组织肉瘤中改善的生存和免疫细胞浸润相关，但与骨肉瘤无关。泛硫乙胺可能是开发抗肿瘤免疫的潜在治疗性免疫佐剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0f4/10583838/d39aca52c6ca/LSA-2023-02200_FigS12.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0f4/10583838/dc00771af61f/LSA-2023-02200_Fig6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0f4/10583838/d39aca52c6ca/LSA-2023-02200_FigS12.jpg

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