Biological modifications of the immune response to COVID-19 vaccine in patients treated with rituximab and immune checkpoint inhibitors
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.
Authors
- Lorenzo Ferrando (ORCID: https://orcid.org/0000-0002-4025-7930)
- Jean‐Charles Grivel (ORCID: https://orcid.org/0000-0003-0365-3181)
- Roberto Massimo Lemoli (ORCID: https://orcid.org/0000-0001-9000-562X)
- Benedetta Cigolini (ORCID: https://orcid.org/0000-0003-1816-9333)
- Filippo Ballerini (ORCID: https://orcid.org/0000-0001-8954-6752)
- Andrea Bellodi (ORCID: https://orcid.org/0000-0002-7519-4458)
- Mario Stabile
- Bianca Bruzzone (ORCID: https://orcid.org/0000-0002-3456-1899)
- Darawan Rinchai (ORCID: https://orcid.org/0000-0001-8851-7730)
- Isabella Lombardo
- Eugenia Montanari
- Pamela Becherini (ORCID: https://orcid.org/0000-0002-8727-0681)
- Fabio Ferrando
- Giusy Gentilcore (ORCID: https://orcid.org/0000-0003-3546-8642)
- Eugenia Cella (ORCID: https://orcid.org/0009-0005-9507-8357)
- Alexander Domnich (ORCID: https://orcid.org/0000-0001-9608-8892)
- Gabriele Zoppoli (ORCID: https://orcid.org/0000-0002-1619-1708)
- Andrea Orsi (ORCID: https://orcid.org/0000-0002-2433-9610)
- Lodovica Zullo (ORCID: https://orcid.org/0000-0002-1659-788X)
- Davide Bedognetti (ORCID: https://orcid.org/0000-0002-5857-773X)
- Neri Fallani
- Martina Dameri (ORCID: https://orcid.org/0000-0001-6898-9247)
- Camilla Scarsi
- Carlo Genova (ORCID: https://orcid.org/0000-0003-3690-8582)
- Alberto Ballestrero (ORCID: https://orcid.org/0000-0002-2601-7711)
- Francesco Ravera (ORCID: https://orcid.org/0000-0003-3856-7910)
- Giulia Francia
- Damien Chaussabel
Institutions
- St. Jude Children's Research Hospital (US)
- Jackson Laboratory (US)
- Ospedale Policlinico San Martino (IT)
- University of Genoa (IT)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-06-19
- DOI
- https://doi.org/10.1016/j.celrep.2025.115838
- Citations
- 1
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- Università degli Studi di Genova
- Associazione Italiana per la Ricerca sul Cancro
- Associazione Italiana Contro le Leucemie-Linfomi e Mieloma
- Alleanza Contro il Cancro