Journal Article Ahead of print
PubMed: 41957474 DOI: 10.1038/s41698-026-01412-2
Terminal T-cell exhaustion predicts tumor control independent of immunotherapy in ovarian cancer.
NPJ Precis Oncol
Authors: Anna Salvioni, Marie Michelas, Mathilde Del, Pierre Vuattoux, Bertille Segier, Clara-Maria Scarlata, Noémie Thébault, Giulia C Leonardi, Nathalie Van Acker, François-Xavier Frenois, Virginie Feliu, Myriam Maixent, Lise Scandella, Sylvie Giuriato, Claire Illac, Sarah Betrian, Charlotte Chollet, Bastien Cabarrou, Carlos Martinez-Gomez, Christel Devaud, Ayman Al Saati, Christine Toulas, Thomas Filleron, Guillaume Bataillon, Jean-Pierre Delord, Maha Ayyoub, Alejandra Martinez
Affiliations
- Université de Toulouse, CNRS, Inserm, Centre de recherches en cancérologie de Toulouse, Toulouse, France.
- Oncopole Claudius Regaud, Institut universitaire du cancer de Toulouse - Oncopole, Toulouse, France.
- Centre Hospitalier Universitaire (CHU), Institut universitaire du cancer de Toulouse - Oncopole, Toulouse, France.
- Biostatistics & Health Data Science units, Institut universitaire du cancer de Toulouse - Oncopole, Toulouse, France.
- Imag'IN Platform, Department of Pathology, Centre Hospitalier Universitaire (CHU), Institut universitaire du cancer de Toulouse - Oncopole, Toulouse, France.
- Université de Toulouse, CNRS, Inserm, Centre de recherches en cancérologie de Toulouse, Toulouse, France.
- Oncopole Claudius Regaud, Institut universitaire du cancer de Toulouse - Oncopole, Toulouse, France.
- Université de Toulouse, CNRS, Inserm, Centre de recherches en cancérologie de Toulouse, Toulouse, France.
- Oncopole Claudius Regaud, Institut universitaire du cancer de Toulouse - Oncopole, Toulouse, France.
Abstract
T-cell exhaustion is typically studied in the context of immune checkpoint blockade, where proliferation and reinvigoration of exhausted cells drives therapeutic responses. However, terminal exhaustion may also represent a marker of chronic tumor-specific activation, raising the possibility that exhausted T cells reflect ongoing endogenous tumor control. Here, we sought to evaluate T-cell exhaustion as a prognostic marker using high-grade serous ovarian cancer (HGSC), an immunotherapy-resistant malignancy, as a model. In a cohort of 80 patients with stage III/IV HGSC, we assessed T-cell infiltration and exhaustion according to homologous recombination (HR) deficiency status. While overall immune infiltration was comparable between HR-deficient and proficient tumors, terminally exhausted CD8 and conventional CD4 T cells were enriched in HR-deficient tumors, where their presence correlated with improved progression-free survival. These findings suggest that exhausted T cells may indicate protective immunity even outside the context of immunotherapy and underscore their prognostic relevance in solid tumors.
MeSH
Cells, Ovary, Neoplasms, Immunotherapy, Ovarian Neoplasms, T-Lymphocytes