Dysregulated inflammation in solid tumor malignancy patients shapes polyfunctional antibody responses to COVID-19 vaccination - Repository

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: https://doi.org/10.1038/s41541-025-01268-w

Abstract

Solid tumor malignancy (STM) patients experience increased risk of breakthrough SARS-CoV-2 infection owing to reduced COVID-19 vaccine immunogenicity. However, the underlying immunological causes of impaired neutralization remain poorly characterized. Furthermore, non-neutralizing antibody functions can contribute to reduced disease severity but remain understudied within high-risk populations. We dissected polyfunctional antibody responses in STM patients and age-matched controls who received adenoviral vector- or mRNA-based COVID-19 vaccine regimens. Elevated inflammatory biomarkers, including agalactosylated IgG, interleukin (IL)-6, IL-18, and an expanded population of CD11c⁻CD21⁻ double negative 3 (DN3) B cells were observed in STM patients and were associated with impaired neutralization. In contrast, mRNA vaccination induced Fc effector functions that were comparable in patients and controls and were cross-reactive against SARS-CoV-2 variants. These data highlight the resilience of Fc functional antibodies and identify systemic inflammatory biomarkers that may underpin impaired neutralizing antibody responses, suggesting potential avenues for immunomodulation via rational vaccine design.

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Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Purcell, R., Koutsakos, M., Kedzierski, L., Allen, L., Lloyd Williams, O., Wang, J., Cavic, G., Wheatley, A., Lee, W., Wines, B., Mark Hogarth, P., Eriksson, E., Mueller, I., Bond, K., Williamson, D., Trevillyan, J., Trubiano, J., Ramanathan, P., Rogerson, S., Arnold, K., Subbarao, K., Lee, A., Hudson, A., Yuile, A., Wheeler, H., Kent, S., Selva, K., Mahanty, S., Kedzierska, K., Fahrer, A., Kanjanapan, Y., Chung, A. & Nguyen, T. 2025, 'Dysregulated inflammation in solid tumor malignancy patients shapes polyfunctional antibody responses to COVID-19 vaccination', npj Vaccines, 10, article no: 217. https://doi.org/10.1038/s41541-025-01268-w

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DOI: https://doi.org/10.1038/s41541-025-01268-w

Repository URI: https://hdl.handle.net/10023/32947