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新生儿 Fc 受体在胰腺癌来源的单核细胞衍生免疫细胞中升高。

The Neonatal Fc Receptor Is Elevated in Monocyte-Derived Immune Cells in Pancreatic Cancer.

机构信息

Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, 496 W. 12th Ave., Columbus, OH 43210, USA.

The James Comprehensive Cancer Center, The Ohio State University, 496 W. 12th Ave., Columbus, OH 43210, USA.

出版信息

Int J Mol Sci. 2022 Jun 25;23(13):7066. doi: 10.3390/ijms23137066.

DOI:10.3390/ijms23137066
PMID:35806069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9266939/
Abstract

The neonatal Fc receptor (FcRn) is responsible for recycling of IgG antibodies and albumin throughout the body. This mechanism has been exploited for pharmaceutic delivery across an array of diseases to either enhance or diminish this function. Monoclonal antibodies and albumin-bound nanoparticles are examples of FcRn-dependent anti-cancer therapeutics. Despite its importance in drug delivery, little is known about FcRn expression in circulating immune cells. Through time-of-flight mass cytometry (CyTOF) we were able to characterize FcRn expression in peripheral blood mononuclear cell (PBMC) populations of pancreatic ductal adenocarcinoma (PDAC) patients and non-cancer donors. Furthermore, we were able to replicate these findings in an orthotopic murine model of PDAC. Altogether, we found that in both patients and mice with PDAC, FcRn was elevated in migratory and resident classical dendritic cell type 2 (cDC2) as well as monocytic and granulocytic myeloid-derived suppressor cell (MDSC) populations compared to tumor-free controls. Furthermore, PBMCs from PDAC patients had elevated monocyte, dendritic cells and MDSCs relative to non-cancer donor PBMCs. Future investigations into FcRn activity may further elucidate possible mechanisms of poor efficacy of antibody immunotherapies in patients with PDAC.

摘要

新生儿 Fc 受体 (FcRn) 负责在全身范围内回收 IgG 抗体和白蛋白。这一机制已被用于多种疾病的药物输送，以增强或减弱这一功能。单克隆抗体和白蛋白结合的纳米颗粒是依赖 FcRn 的抗癌治疗药物的例子。尽管它在药物输送中的重要性，但人们对循环免疫细胞中 FcRn 的表达知之甚少。通过飞行时间质谱流式细胞术 (CyTOF)，我们能够描述胰腺导管腺癌 (PDAC) 患者和非癌症供体的外周血单核细胞 (PBMC) 群体中的 FcRn 表达。此外，我们能够在 PDAC 的原位小鼠模型中复制这些发现。总的来说，我们发现与无肿瘤对照相比，在 PDAC 患者和小鼠中，迁移和驻留的经典树突状细胞 2 (cDC2) 以及单核细胞和粒细胞髓源性抑制细胞 (MDSC) 群体中的 FcRn 升高。此外，与非癌症供体 PBMC 相比，PDAC 患者的 PBMC 中单核细胞、树突状细胞和 MDSC 升高。对 FcRn 活性的进一步研究可能会进一步阐明 PDAC 患者抗体免疫疗法疗效不佳的可能机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/aeb59e3cef18/ijms-23-07066-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/47a1c52fb93d/ijms-23-07066-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/3ca37103e5c0/ijms-23-07066-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/b0cfe30ae2d5/ijms-23-07066-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/2a73651595bd/ijms-23-07066-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/aeb59e3cef18/ijms-23-07066-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/47a1c52fb93d/ijms-23-07066-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/3ca37103e5c0/ijms-23-07066-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17aa/9266939/b0cfe30ae2d5/ijms-23-07066-g003.jpg
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