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<p>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.</p>

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Terminal T-cell exhaustion predicts tumor control independent of immunotherapy in ovarian cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月10日

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  • 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

摘要

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.