Ray-Coquard I, Kaminsky-Forrett MC, Ohkuma R, de Montfort A, Joly F, Treilleux I, Ghamry-Barrin S, Bello-Roufai D, Saintigny P, Angelergues A, Michon L, Hardy-Bessard AC, Attignon V, Auclair J, Chemin G, Lainé A, Péré H, Veyer D, Savoye AM, Berthet J, Caux C, Lecuru F, Dubois B, Bétrian S.
Nat Commun . 2026 Jan 5;17(1):922
doi: 10.1038/s41467-025-67646-z.
PMID: 41490885
ABSTRACT
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+/FOXP3+ cell ratio (primary endpoint; increase of 0.87 cells/mm², P = 0.0164) and proliferative CD8+ 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.
