美国俄克拉荷马大学Min Li等研究人员合作发现，巨噬细胞与癌细胞之间的交流增强胰腺癌的恶病质。2024年4月11日，《癌细胞》杂志在线发表了这项成果。

研究人员发现，巨噬细胞通过促进肿瘤分泌TWEAK（类TNF弱凋亡诱导因子），在增强胰腺癌诱导的肌肉萎缩中的关键作用。具体来说，消耗巨噬细胞可逆转肿瘤细胞诱导的肌肉退化。巨噬细胞通过CCL5/TRAF6/NF-κB途径诱导TWEAK的非自主分泌。TWEAK通过激活MuRF1启动肌肉重塑，促进肌肉萎缩。

值得注意的是，肿瘤细胞通过CCL2/CCR2轴招募巨噬细胞并对其进行重编程，破坏巨噬细胞和肿瘤细胞之间的相互作用可减轻肌肉萎缩。

总之，这项研究确定了胰腺癌细胞和巨噬细胞之间的前馈环路，它是肿瘤细胞非自主性激活TWEAK分泌的基础，从而为胰腺癌恶病质提供了有希望的治疗靶点。

据悉，由于治疗方案有限，恶病质仍是癌症患者面临的一大挑战。研究肿瘤细胞与免疫微环境之间相互作用的特征，可能有助于确定癌症恶病质的潜在治疗靶点。

附：英文原文

Title: The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia

Author: Mingyang Liu, Yu Ren, Zhijun Zhou, Jingxuan Yang, Xiuhui Shi, Yang Cai, Alex X. Arreola, Wenyi Luo, Kar-Ming Fung, Chao Xu, Ryan D. Nipp, Michael S. Bronze, Lei Zheng, Yi-Ping Li, Courtney W. Houchen, Yuqing Zhang, Min Li

Issue&Volume: 2024-04-11

Abstract: With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells recruit and reprogram macrophages via the CCL2/CCR2 axis and disrupting the interplay between macrophages and tumor cells attenuates muscle wasting. Collectively, this study identifies a feedforward loop between pancreatic cancer cells and macrophages, underlying the non-autonomous activation of TWEAK secretion from tumor cells thereby providing promising therapeutic targets for pancreatic cancer cachexia.

DOI: 10.1016/j.ccell.2024.03.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(24)00094-1