Publications

2025

1. TIE-2-expressing monocytic myeloid-derived suppressor cells are involved in resistance to anti-PD-1 therapy mediated by angiopoietin 2 in patients with melanoma

   Amélie Marguier, Jessica Mathiot, Babacar NDao, Mylène Wespiser, Victor Pereira, Benoı̂t Lecoester, Laura Boullerot, Marine Malfroy, Caroline Laheurte, François Aubin, Olivier Adotevi, and Charlée Nardin

   J. Invest. Dermatol., Oct 2025
2. IF 10.6, Q1

   

   UCPVax, a CD4 helper peptide vaccine, induces polyfunctional Th1 cells, antibody response, and epitope spreading to improve antitumor immunity

   Caroline Laheurte, Laura Boullerot, Babacar Ndao, Marine Malfroy, Lise Queiroz, Phillippe Guillaume, Romain Loyon, Evan Seffar, Eleonore Gravelin, Adeline Renaudin, Marion Jacquin, Aurélia Meurisse, Dewi Vernerey, François Ghiringhelli, Yann Godet, Raphael Genolet, Camilla Jandus, Christophe Borg, and Olivier Adotévi

   Cell Rep. Med., Jul 2025

   Abstract Pubmed DOI

   The induction of an antitumor CD4+ T helper response is essential for the efficacy of therapeutic cancer vaccines. However, few vaccines are specifically designed to target CD4+ T cells in human cancers. Here, we characterize the immune mechanisms of UCPVax, a helper peptide vaccine derived from telomerase. Ex vivo immune profiling of peripheral blood from 60 patients with advanced lung cancer reveals that UCPVax selectively activates CD4+ T cells in vivo across a broad HLA-DR restriction. The vaccine elicits a synergistic immune triad, including cytokine polyfunctional CD4+ Th1 cells, epitope spreading, and antibody response, contributing to effective tumor control. Single-cell analysis further demonstrates that UCPVax drives CD4+ T cells toward effector memory and cytolytic differentiation. Thus, vaccine-induced CD4+ T cells trigger broad and durable antitumor immunity. These findings highlight UCPVax as an off-the-shelf helper platform to enhance therapeutic cancer vaccine efficacy. This study was registered at ClinicalTrials.gov: NCT02818426.

3. Characterization of the aryl hydrocarbon receptor as a potential candidate to improve cancer T cell therapies

   Valentine De Castro, Oumaı̈ma Abdellaoui, Barbara Dehecq, Babacar Ndao, Patricia Mercier-Letondal, Alexandra Dauvé, Francine Garnache-Ottou, Olivier Adotévi, Romain Loyon, and Yann Godet

   Cancer Immunol. Immunother., May 2025

   Abstract

   The efficacy of T-cell-based cancer therapies can be limited by the tumor microenvironment which can lead to T cell dysfunction. Multiple studies, particularly in murine models, have demonstrated the capacity of the aryl hydrocarbon receptor (AHR) to negatively regulate antitumor T cell functions. AHR is a cytoplasmic receptor and transcription factor that was originally identified as a xenobiotic sensor, but has since been shown to play a significant role in the gene regulation of various immune cells, including T cells. Given the insights from murine studies, AHR emerges as a promising candidate to invalidate for optimizing T cell-based cancer therapies. However, the controversial role of AHR in human T cells underscores the need for a more comprehensive characterization of AHR expressing T cells. This study aims to investigate the regulatory mechanisms of AHR in human T cell biology to better understand its impact on reducing antitumor immune responses. Here, we knocked-out AHR in human T cells using CRISPR-Cas9 technology to characterize AHR’s function in an in vitro chronic stimulation model. Engineered T cells exhibited enhanced effector- and memory-like profiles and expressed reduced amount of CD39 and TIGIT. AHR knockout enhanced human CAR-T cells’ functionality and persistence upon tumor chronic stimulation. Collectively, these results highlight the role of AHR in human CAR-T cells efficiency.