This data published in Nature this summer emphasizes to me the importance of immune modulation potentially over a long period of time in that dormant cancer cells can be re-activated through an IL-6 dependent mechanism in response to influenza and SARS COVID infections which trigger an inflammatory response and cascading t-cell changes. We have very intriguing data on cancer impacting long term survival but completely unanswered IMHO based on this article is how long this treatment should remain in place…or would it be episodic following complete response and resolution of all identified tumor masses? This is not likely to be solved until post-approval use in the real world. Clearly not a one and done treatment for cancer, Leronlimab dosing may be required for a sustained period of time which would have revenue ramifications. There are obvious cross-over implications with the long acting option still undergoing development.
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.”
https://www.nature.com/articles/s41586-025-09332-0
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.”
https://www.nature.com/articles/s41586-025-09332-0
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