Biological modifications of the immune response to COVID-19 vaccine in patients treated with rituximab and immune checkpoint inhibitors

作者：Francesco Ravera, Martina Dameri, Isabella Lombardo, Mario Stabile, Pamela Becherini, Neri Fallani, Camilla Scarsi, Benedetta Cigolini, Giusy Gentilcore, Alexander Domnich, Lodovica Zullo, Eugenia Cella, Giulia Francia, Eugenia Montanari, Andrea Orsi, Andrea Bellodi, Fabio Ferrando, Darawan Rinchai, Filippo Ballerini, Bianca Bruzzone, Damien Chaussabel, Jean‐Charles Grivel, Carlo Genova, Roberto M. Lemoli, Davide Bedognetti, Alberto Ballestrero, Lorenzo Ferrando, Gabriele Zoppoli · 发表于：Cell Reports · 年份：2025 · DOI：10.1016/j.celrep.2025.115838 · 被引用次数：3 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

Understanding how immune-modulating therapies affect mRNA vaccine responses is essential for optimizing immunization strategies in cancer and immunocompromised patients. In this work, we investigate the immune response to the third dose of COVID-19 mRNA vaccine in cancer-free individuals, patients with non-Hodgkin lymphoma treated with rituximab (RTX), and patients with solid tumors receiving immune checkpoint inhibitors (ICIs). By integrating blood RNA sequencing, SARS-CoV-2 serology, and interferon-γ release assessment, we chart the vaccine-induced immunity over a 6-month time frame. Our findings reveal that RTX-treated patients exhibit profound immune dysfunction, characterized by a blunted type I interferon response, upregulation of transcripts pertaining to regulatory T cells, and widespread impairment of humoral immunity. In contrast, ICI-treated patients have preserved vaccine-induced immunity, displaying adaptive B cell and T cell responses akin to those of cancer-free volunteers. These results provide critical insights into immunization strategies for immunocompromised populations and may inform future vaccination protocols.