Impact of chemotherapy on humoral and cellular immune responses to COVID-19 vaccination in patients with solid tumors

Introduction: Despite SARS-CoV-2 pandemic has subsided, vaccine response profiling in patients with cancer remains critical. Methods: 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. Results: 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. Discussion: 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.