美国斯坦福大学Edgar G. Engleman、Nathan E. Reticker-Flynn等研究人员合作发现，淋巴结定植诱导肿瘤免疫耐受来促进远处转移。这一研究成果于2022年5月6日在线发表在国际学术期刊《细胞》上。
研究人员建立了一个淋巴结（LN）转移的合成黑色素瘤小鼠模型，以研究肿瘤如何扩散到LN，以及LN定植是否影响到远处组织的转移。结果表明，通过一个表观遗传灌输的肿瘤内在干扰素反应程序，使得NK细胞的逃避和促进LN定植，并赋予了LN转移潜力的增强。LN转移抵制T细胞介导的细胞毒性，诱导抗原特异性调节性T细胞，并产生肿瘤特异性免疫耐受，随后促进远处肿瘤的定植。这些效应延伸到人类癌症和其他小鼠癌症模型，暗示了恶性肿瘤扩散到远处器官的保守系统性机制。
据悉，对于许多实体恶性肿瘤来说，LN受累是远处转移疾病的预兆，因此也是一个重要的预后因素。除了作为生物标志物的效用外，LN转移是否以及如何在形成远处转移中发挥积极作用仍然是一个开放的问题。
附：英文原文
Title: Lymph node colonization induces tumor-immune tolerance to promote distant metastasis
Author: Nathan E. Reticker-Flynn, Weiruo Zhang, Julia A. Belk, Pamela A. Basto, Nichole K. Escalante, Genay O.W. Pilarowski, Alborz Bejnood, Maria M. Martins, Justin A. Kenkel, Ian L. Linde, Sreya Bagchi, Robert Yuan, Serena Chang, Matthew H. Spitzer, Yaron Carmi, Jiahan Cheng, Lorna L. Tolentino, Okmi Choi, Nancy Wu, Christina S. Kong, Andrew J. Gentles, John B. Sunwoo, Ansuman T. Satpathy, Sylvia K. Plevritis, Edgar G. Engleman
Issue&Volume: 2022-05-06
Abstract: For many solid malignancies, lymph node (LN) involvement represents a harbinger ofdistant metastatic disease and, therefore, an important prognostic factor. Beyondits utility as a biomarker, whether and how LN metastasis plays an active role inshaping distant metastasis remains an open question. Here, we develop a syngeneicmelanoma mouse model of LN metastasis to investigate how tumors spread to LNs andwhether LN colonization influences metastasis to distant tissues. We show that anepigenetically instilled tumor-intrinsic interferon response program confers enhancedLN metastatic potential by enabling the evasion of NK cells and promoting LN colonization.LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatoryT cells, and generate tumor-specific immune tolerance that subsequently facilitatesdistant tumor colonization. These effects extend to human cancers and other murinecancer models, implicating a conserved systemic mechanism by which malignancies spreadto distant organs.
DOI: 10.1016/j.cell.2022.04.019
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00466-4