학술논문
Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs.
Document Type
Author
Chia SB; University of Colorado Anschutz Medical Campus.; Johnson BJ; University of Colorado Anschutz Medical Campus.; Hu J; University of Colorado Anschutz Medical Campus.; Vermeulen R; Utrecht University.; Chadeau-Hyam M; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK.; Guntoro F; Imperial College London.; Montgomery H; University College London.; Boorgula MP; University of Colorado.; Sreekanth V; University of Colorado Anschutz Medical Campus.; Goodspeed A; University of Colorado Anschutz Medical Campus.; Davenport B; University of Colorado Anschutz Medical Campus.; Pereira FV; University of Colorado Anschutz Medical Campus.; Zaberezhnyy V; University of Colorado Anschutz Medical Campus.; Schleicher WE; University of Colorado Anschutz Medical Campus.; Gao D; Biostatistics and Bioinformatics Core, University of Colorado Cancer Center.; Cadar AN; University of Connecticut.; Papanicolaou M; Albert Einstein College of Medicine.; Beheshti A; Broad Institute.; Baylin SB; Johns Hopkins Medical Institutions.; Costello J; University of Colorado Anschutz Medical Campus.; Bartley JM; University of Connecticut.; Morrison TE; University of Colorado.; Aguirre-Ghiso JA; Albert Einstein College of Medicine.; Rincon M; University of Colorado Anschutz Medical Campus.; DeGregori J; University of Colorado Anschutz Medical Campus.
Source
Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy 1 . Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically 2,3 . Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks. Such DCC phenotypic change and expansion is interleukin-6 (IL-6)-dependent. We further show that CD4 T cells are required for the maintenance of pulmonary metastatic burden post-influenza virus infection, in part through attenuation of CD8 cell responses in the lungs. Single-cell RNA-seq analyses reveal DCC-dependent impairment of T-cell activation in the lungs of infected mice. SARS-CoV-2 infected mice also showed increased breast DCC expansion in lungs post-infection. Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer-related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis.
Competing Interests: Additional Declarations: Yes there is potential Competing Interest. HM has consulted Astra Zeneca relating to the use of monoclonal antibodies in the prevention and treatment of SARS-CoV-2 infection. J.A.A-G is a scientific co-founder, scientific advisory board member and equity owner in HiberCell and receives financial compensation as a consultant for HiberCell, a Mount Sinai spin-off company focused on the research and development of therapeutics that prevent or delay the recurrence of cancer. J.A.A-G is also a consultant for Astrin Biosciences, Inc and chief mission officer of Samuel Waxman Cancer Research Foundation.
Competing Interests: Additional Declarations: Yes there is potential Competing Interest. HM has consulted Astra Zeneca relating to the use of monoclonal antibodies in the prevention and treatment of SARS-CoV-2 infection. J.A.A-G is a scientific co-founder, scientific advisory board member and equity owner in HiberCell and receives financial compensation as a consultant for HiberCell, a Mount Sinai spin-off company focused on the research and development of therapeutics that prevent or delay the recurrence of cancer. J.A.A-G is also a consultant for Astrin Biosciences, Inc and chief mission officer of Samuel Waxman Cancer Research Foundation.