Predictive model for BNT162b2 vaccine response in cancer patients based on blood cytokines and growth factors

Angelina Konnova, Fien H R De Winter, Akshita Gupta, Lise Verbruggen, An Hotterbeekx, Matilda Berkell, Laure-Anne Teuwen, Greetje Vanhoutte, Bart Peeters, Silke Raats, Isolde Van der Massen, Sven De Keersmaecker, Yana Debie, Manon Huizing, Pieter Pannus, Kristof Y Neven, Kevin Ariën, Geert A Martens, Marc Van Den Bulcke, Ella RoelantIsabelle Desombere, Sébastien Anguille, Zwi Berneman, Maria E Goossens, Herman Goossens, Surbhi Malhotra-Kumar, Evelina Tacconelli, Timon Vandamme, Marc Peeters, Peter van Dam, Samir Kumar-Singh

Research output: Contribution to journalA1: Web of Science-articlepeer-review

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Background: Patients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed.

Methods: We employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine.

Results: C-reactive protein (general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) correctly classified patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments.

Conclusion: We propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at persistent high risk of COVID-19 despite vaccination with BNT162b2. Our data also suggest that such a signature may reflect the inherent immunological constitution of some cancer patients who are refractive to immunotherapy.

Original languageEnglish
Article number1062136
JournalFrontiers in Immunology
Number of pages10
Publication statusPublished - 2022


  • Humans
  • BNT162 Vaccine/immunology
  • COVID-19/prevention & control
  • Cytokines/blood
  • Intercellular Signaling Peptides and Proteins
  • Neoplasms


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