武汉大学教授Wei Song团队近期取得重要工作进展，他们研究发现肾脏NF-κB活化损害尿酸稳态以促进与消瘦无关的肿瘤相关死亡率。这一研究成果2022年8月26日在线发表于《免疫学》杂志上。

研究人员报告了携带恶性yki^3SA-肠道肿瘤的果蝇，它们表现出共生细菌的指数增加，这些细菌主要是从环境中获得的，并且由于抑制肠道抗菌酰胺酶PGRP-SC2而导致全身性IMD-NF-κB活化。消除肠道微生物或阻断肾样马氏管中的特异性IMD-NF-κB可以有效地提高携带yki^3SA肿瘤果蝇的死亡率，其方式与宿主消瘦无关。研究人员进一步表明，肾脏IMD-NF-κB激活导致尿酸（UA）超载，从而降低了荷瘤果蝇的存活率。因此，他们的研究结果揭示了一种基本机制，即肠道共生失调、肾脏免疫激活和UA失衡会加剧肿瘤相关的宿主死亡。

据介绍，肿瘤引起的宿主消瘦和死亡是跨物种的普遍现象。许多小组先前已经证明了恶性肿瘤对啮齿动物和果蝇宿主消瘦的内分泌影响。然而，环境因素和宿主免疫反应是否以及如何促进肿瘤相关的宿主消耗和存活，在很大程度上是未知的。

附：英文原文

Title: Renal NF-κB activation impairs uric acid homeostasis to promote tumor-associated mortality independent of wasting

Author: Yuchen Chen, Wenhao Xu, Yuan Chen, Anxuan Han, Jiantao Song, Xiaoya Zhou, Wei Song

Issue&Volume: 2022-08-26

Abstract: Tumor-induced host wasting and mortality are general phenomena across species. Many groups have previously demonstrated endocrinal impacts of malignant tumors on host wasting in rodents and Drosophila. Whether and how environmental factors and host immune response contribute to tumor-associated host wasting and survival, however, are largely unknown. Here, we report that flies bearing malignant yki3SA-gut tumors exhibited the exponential increase of commensal bacteria, which were mostly acquired from the environment, and systemic IMD-NF-κB activation due to suppression of a gut antibacterial amidase PGRP-SC2. Either gut microbial elimination or specific IMD-NF-κB blockade in the renal-like Malpighian tubules potently improved mortality of yki3SA-tumor-bearing flies in a manner independent of host wasting. We further indicate that renal IMD-NF-κB activation caused uric acid (UA) overload to reduce survival of tumor-bearing flies. Therefore, our results uncover a fundamental mechanism whereby gut commensal dysbiosis, renal immune activation, and UA imbalance potentiate tumor-associated host death.

DOI: 10.1016/j.immuni.2022.07.022

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00357-0