AUTHOR=Konnova Angelina , De Winter Fien H. R. , Gupta Akshita , Verbruggen Lise , Hotterbeekx An , Berkell Matilda , Teuwen Laure-Anne , Vanhoutte Greetje , Peeters Bart , Raats Silke , Massen Isolde Van der , De Keersmaecker Sven , Debie Yana , Huizing Manon , Pannus Pieter , Neven Kristof Y. , Ariën Kevin K. , Martens Geert A. , Bulcke Marc Van Den , Roelant Ella , Desombere Isabelle , Anguille Sébastien , Berneman Zwi , Goossens Maria E. , Goossens Herman , Malhotra-Kumar Surbhi , Tacconelli Evelina , Vandamme Timon , Peeters Marc , van Dam Peter , Kumar-Singh Samir TITLE=Predictive model for BNT162b2 vaccine response in cancer patients based on blood cytokines and growth factors JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1062136 DOI=10.3389/fimmu.2022.1062136 ISSN=1664-3224 ABSTRACT=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.