Guan Xu, Zhang Yueyang, Sun Ruifang, Wang Guiyu, Bi Xiaoman, Zhang Zhen, Zan Likun, Meng Yongsheng, Liu Yunxiao, Guo Jinyuan, Ma Jian, Li Jiale, Hu Hanqing, Zhang Yixun, Zhang Xin, Liu Maoxi, Jiang Bo, Liu Haiyi, Zou Shuangmei, Xi Yanfeng, Zhou Haitao, Bai Wenqi, Wu Deng, Wang Xishan
Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Colorectal Surgery, Shanxi Province Cancer Hospital, Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
Nat Commun. 2025 Aug 22;16(1):7834. doi: 10.1038/s41467-025-63200-z.
Lymph nodes (LNs) play a pivotal role in colorectal cancer (CRC) progression and immunity, yet their molecular and functional diversity remains poorly understood. By analyzing 630 LNs and 88 primary tumors from 200 CRC patients across four independent cohorts using bulk and single-cell RNA sequencing, we identify four non-metastatic negative LNs (NLN) subtypes (NLN_C1-C4) exhibiting obviously different immune function and stromal expansion. NLN_C3/C4 are characterized by diminished T and B cell activity and fibroblast-driven fibrosis, with follicular dendritic cell loss contributing to B cell dysfunction. Immune checkpoint inhibitors partially reverse these effects, restoring FDC and B cell activity. LNs subtypes demonstrate heterogeneity across patients and within individuals, with higher NLN_C3/C4 proportions associated with advanced tumor stages, poorer survival, and recurrence. Here, we report LNs subtypes as critical manifestations of LN heterogeneity in CRC, providing a basis for improved clinical stratification and LN-targeted therapeutic strategies.
淋巴结（LNs）在结直肠癌（CRC）进展和免疫中起关键作用，但其分子和功能多样性仍知之甚少。通过使用批量和单细胞RNA测序分析来自四个独立队列的200例CRC患者的630个淋巴结和88个原发性肿瘤，我们鉴定出四种非转移性阴性淋巴结（NLN）亚型（NLN_C1 - C4），它们表现出明显不同的免疫功能和基质扩张。NLN_C3/C4的特征是T细胞和B细胞活性降低以及成纤维细胞驱动的纤维化，滤泡树突状细胞的丧失导致B细胞功能障碍。免疫检查点抑制剂部分逆转这些效应，恢复滤泡树突状细胞和B细胞活性。淋巴结亚型在患者之间和个体内部表现出异质性，NLN_C3/C4比例较高与肿瘤晚期、较差的生存率和复发相关。在这里，我们报告淋巴结亚型是CRC中淋巴结异质性的关键表现，为改善临床分层和淋巴结靶向治疗策略提供了基础。
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