ORIGINAL RESEARCH article
Front. Immunol.
Sec. Immunological Memory
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1664072
Impact of Chemotherapy on Humoral and Cellular Immune Responses to COVID-19 Vaccination in Patients with Solid Tumors
Provisionally accepted
Andrea Favalli1
Giorgio Patelli2,3
Paola Gruarin1
Andrea Gobbini1
Elisa Pesce4
Sara Mariano3
Mauro Bombaci1Francesca Vincenti1
Lorena Donnici1Silvia Marchese1,5Daniele Piscazzi2,3
Alessio Amatu3Federica Tosi3Silvia Ghezzi3
Arianna Pani2Silvia Principato1
Andrea Lombardi6,7
Alessandra Bandera6,7
Sergio Abrignani1Salvatore Siena2,3
Andrea Sartore-Bianchi2,3*
Renata Maria Grifantini1*- 1Fondazione Istituto Nazionale Genetica Molecolare, Milan, Italy
- 2Department of Oncology and Hematology Oncology, Faculty of Medicine and Surgery, University of Milan, Milan, Italy
- 3ASST Grande Ospedale Metropolitano Niguarda Dipartimento Funzionale Niguarda Cancer Center, Milan, Italy
- 4Department of Clinical Sciences and Community Health milan, Milan, Italy
- 5Universita degli Studi di Milano Dipartimento di Scienze Farmacologiche e Biomolecolari, Milan, Italy
- 6Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Reparto Malattie Infettive, Milan, Italy
- 7Universita degli Studi di Milano Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Milan, Italy
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Despite SARS-CoV-2 pandemic has subsided, vaccine response profiling in patients with cancer remains critical. We longitudinally assessed humoral and cellular immunity in adults with solid tumours treated with chemotherapy (ChT) or non-ChT regimens after two mRNA vaccine doses plus booster, compared with vaccinated cancer-free controls, naturally infected (convalescent) subjects including both patients with cancer and cancer-free individuals, and unvaccinated/uninfected individuals with or without cancer as a baseline reference. Anti-Spike IgG titres matched cancer-free controls, but anti-RBD titres and neutralising activity were consistently lower in cancer post-vaccination, most markedly with ChT, and declined faster over 4-6 months. Boosters restored IgG, yet gains were smaller in ChT recipients. Cellular analyses revealed sustained and booster-enhanced Spike-specific B cells in all groups; however, ChT exposure was associated with reduced CD27 expression on these cells, suggesting impaired activation and memory maturation. These findings support tailored immune monitoring and vaccination strategies in oncology and identify CD27 downregulation as a novel B-cell dysfunction detected by high-dimensional immunophenotyping.
Keywords: solid tumors, SARS-CoV-2, vaccinations, seroconversion, memory B cells, High-dimensional, unbiased immunophenotyping
Received: 11 Jul 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Favalli, Patelli, Gruarin, Gobbini, Pesce, Mariano, Bombaci, Vincenti, Donnici, Marchese, Piscazzi, Amatu, Tosi, Ghezzi, Pani, Principato, Lombardi, Bandera, Abrignani, Siena, Sartore-Bianchi and Grifantini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Andrea Sartore-Bianchi, Department of Oncology and Hematology Oncology, Faculty of Medicine and Surgery, University of Milan, Milan, Italy
Renata Maria Grifantini, Fondazione Istituto Nazionale Genetica Molecolare, Milan, Italy
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