近日，美国科罗拉多大学安舒茨医学院教授James DeGregori及其团队的研究认为呼吸道病毒感染唤醒肺部转移性乳腺癌细胞。相关论文发表在2025年7月30日出版的《自然》杂志上。

在这里，该研究组在小鼠中证明，流感和SARS-CoV-2感染导致肺部乳腺DCC的前休眠表型丧失，在感染后几天内引导DCC增殖，并在两周内癌细胞大量扩增为转移性病变。这些表型转变和扩增依赖于白细胞介素-6。该研究团队发现，DCC损害肺T细胞活化，CD4⁺ T细胞通过抑制CD8⁺ T细胞活化和细胞毒性来维持流感感染后肺转移负荷。至关重要的是，这些实验结果与人类观测数据一致。对来自UK Biobank（所有癌症）和Flatiron Health（乳腺癌）数据库的癌症幸存者的分析显示，与未感染的癌症幸存者相比，SARS-CoV-2感染大大增加了癌症相关死亡率和肺转移的风险。这些发现强调了呼吸道病毒感染对转移性癌症复发的巨大影响，为感染性疾病与癌症转移之间的联系提供了新的见解。

据介绍，乳腺癌是全球第二大常见癌症，大多数死亡是由转移性疾病引起的，通常是在长时间的临床休眠之后。了解破坏休眠播散性癌细胞（DCCs）休眠的机制对于解决转移进展至关重要。由流感和SARS-CoV-2等呼吸道病毒引起的感染会引发局部和全身炎症。

附：英文原文

Title: Respiratory viral infections awaken metastatic breast cancer cells in lungs

Author: Chia, Shi B., Johnson, Bryan J., Hu, Junxiao, Valena-Pereira, Felipe, Chadeau-Hyam, Marc, Guntoro, Fernando, Montgomery, Hugh, Boorgula, Meher P., Sreekanth, Varsha, Goodspeed, Andrew, Davenport, Bennett, De Dominici, Marco, Zaberezhnyy, Vadym, Schleicher, Wolfgang E., Gao, Dexiang, Cadar, Andreia N., Petriz-Otao, Lucia, Papanicolaou, Michael, Beheshti, Afshin, Baylin, Stephen B., Guarnieri, Joseph W., Wallace, Douglas C., Costello, James C., Bartley, Jenna M., Morrison, Thomas E., Vermeulen, Roel, Aguirre-Ghiso, Julio A., Rincon, Mercedes, DeGregori, James

Issue&Volume: 2025-07-30

Abstract: Breast cancer is the second most common cancer globally, with most deaths caused by metastatic disease, often following long periods of clinical dormancy1. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCCs) is crucial for addressing metastatic progression. Infections caused by respiratory viruses such as influenza and SARS-CoV-2 trigger both local and systemic inflammation2,3. Here we demonstrate, in mice, that influenza and SARS-CoV-2 infections lead to loss of the pro-dormancy phenotype in breast DCCs in the lung, causing DCC proliferation within days of infection and a massive expansion of carcinoma cells into metastatic lesions within two weeks. These phenotypic transitions and expansions are interleukin-6 dependent. We show that DCCs impair lung T cell activation and that CD4+ T cells sustain the pulmonary metastatic burden after the influenza infection by inhibiting CD8+ T cell activation and cytotoxicity. Crucially, these experimental findings align with human observational data. Analyses of cancer survivors from the UK Biobank (all cancers) and Flatiron Health (breast cancer) databases reveal that SARS-CoV-2 infection substantially increases the risk of cancer-related mortality and lung metastasis compared with uninfected cancer survivors. These discoveries underscore the huge impact of respiratory viral infections on metastatic cancer resurgence, offering new insights into the connection between infectious diseases and cancer metastasis.

DOI: 10.1038/s41586-025-09332-0

Source: https://www.nature.com/articles/s41586-025-09332-0