Neoadjuvant immune checkpoint blockade before chemoradiation for cervical squamous carcinoma (GINECO window-of-opportunity COLIBRI study): a phase II trial
Combining immunotherapy with chemoradiation is effective in locally advanced cervical cancer. However, the impact of induction combination immunotherapy on immune modulation and treatment response is poorly understood. In this phase II trial (NCT04256213), 40 females with locally advanced cervical carcinoma received one cycle of nivolumab-plus-ipilimumab immunotherapy before standard chemoradiation, followed by maintenance nivolumab. We show, using multiplex-immunofluorescence tissue imaging, a significantly increased CD8<sup>+</sup>/FOXP3<sup>+</sup> cell ratio (primary endpoint; increase of 0.87 cells/mm², P = 0.0164) and proliferative CD8<sup>+</sup> T-cell density after one cycle of combination immunotherapy. HOT score (27-gene-based signature identifying immunologically active tumors) also increased significantly (exploratory analysis; 0.17, P < 0.0001). Objective response rates (secondary endpoint) were 13% immediately after combination immunotherapy, 98% (65% complete response) after chemoradiation, and 90% at treatment completion. High HOT score at baseline and immune changes induced by combination immunotherapy were associated with complete response at treatment completion. Induction immunotherapy may prime tumors for improved response to standard therapy.
Authors
- Gabriel Chemin (ORCID: https://orcid.org/0009-0003-6979-3037)
- Lucas Michon (ORCID: https://orcid.org/0000-0002-1839-4656)
- Bertrand Dubois (ORCID: https://orcid.org/0000-0002-7859-4975)
- Isabelle Treilleux
- Alexandra Lainé (ORCID: https://orcid.org/0000-0002-8367-6115)
- Ryotaro Ohkuma (ORCID: https://orcid.org/0000-0003-4121-2491)
- Aymeric de Montfort
- Antoine Angelergues (ORCID: https://orcid.org/0009-0005-4876-918X)
- Marie-Christine Kaminsky-Forrett
- Aude-Marie Savoye (ORCID: https://orcid.org/0000-0003-0026-4084)
- Diana Bello-Roufai
- Hélène Péré (ORCID: https://orcid.org/0000-0002-3225-4238)
- Justine Berthet (ORCID: https://orcid.org/0000-0001-6096-263X)
- Valéry Attignon (ORCID: https://orcid.org/0000-0002-1529-0595)
- Jessie Auclair
- Christophe Caux
- Pierre Saintigny
- Anne-Claire Hardy-Bessard
- Fabrice Lecuru
- Sarah Ghamry-Barrin
- Isabelle Ray-Coquard
- Sarah Bétrian
- Florence Joly
- David Veyer
Institutions
- Université Claude Bernard Lyon 1 (FR)
- École Normale Supérieure de Lyon (FR)
- SHOWA Medical University (JP)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Paris Cité (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institut de Cancérologie de Lorraine (FR)
- Centre François Baclesse (LU)
- Centre Léon Bérard (FR)
- Hôpital Européen (FR)
- Groupe Hospitalier Diaconesses Croix Saint-Simon (FR)
- Centre François Baclesse (FR)
- Centre de Recherche en Cancérologie de Lyon (FR)
- Institut Claudius Regaud (FR)
- Arcagy Gineco (FR)
- Génomique Fonctionnelle des Tumeurs Solides (FR)
- Institut Jean Godinot (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-05
- DOI
- https://doi.org/10.1038/s41467-025-67646-z
- Primary Topic
- Endometrial and Cervical Cancer Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bristol-Myers Squibb
- Institut National de la Santé et de la Recherche Médicale
- Institut National Du Cancer
- Direction Générale de l’offre de Soins
- Servier
- Centre Léon Bérard
- National Cancer Institute