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<p>Tumor-infiltrating lymphocyte (TIL)-therapy has received FDA approval for the treatment of advanced melanoma and shows potential for broader applications in solid tumors, including glioblastoma. In this study, tumor-reactive TILs (tr-TILs) are isolated and enriched for CD137 expression from cavitron ultrasonic aspirator (CUSA) emulsions of 161 adult patients diagnosed with diffuse gliomas. Tr-TILs are successfully expanded in 87 out of the 161 patients, reflecting an expansion rate of 54%. Notably, the presence of IDH1 mutation and the cumulative dose of steroids are identified as significant negative predictors of expansion efficacy. The expanded tr-TILs exhibit distinct phenotypic and molecular dysfunctional features yet show upregulated expression of progenitor/memory-like markers and polyclonal T-cell receptors. Importantly, these tr-TILs demonstrate specific antitumor reactivity against autologous tumor cells in both in vitro and in vivo xenograft models. These findings provide a compelling background for a personalized immunotherapeutic approach while tackling one of the most significant challenges in oncology.</p>

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Polyclonal expansion of functional tumor-reactive lymphocytes infiltrating glioblastoma for personalized cell therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月25日

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  • Martina Maffezzini,
  • Silvia Musio,
  • Natalia Di Ianni,
  • Agnese Rumolo,
  • Monica Patanè,
  • Andrea Galluzzo,
  • Irene Sambruni,
  • Arianna Berlendis,
  • Domenico Aquino,
  • Giacomo Baso,
  • Manuela Zingarelli,
  • Manuel Facciolla,
  • Luisa Maddaloni,
  • Rossella Valentino,
  • Rosina Paterra,
  • Fabio Agistri,
  • Mariangela Farinotti,
  • Luca Mattei,
  • Paola Coluccia,
  • Francesco Acerbi,
  • Francesco DiMeco,
  • Bianca Pollo,
  • Antonio Silvani,
  • Marica Eoli,
  • Catia Traversari,
  • Daniela Montagna,
  • Serena Pellegatta

摘要

Tumor-infiltrating lymphocyte (TIL)-therapy has received FDA approval for the treatment of advanced melanoma and shows potential for broader applications in solid tumors, including glioblastoma. In this study, tumor-reactive TILs (tr-TILs) are isolated and enriched for CD137 expression from cavitron ultrasonic aspirator (CUSA) emulsions of 161 adult patients diagnosed with diffuse gliomas. Tr-TILs are successfully expanded in 87 out of the 161 patients, reflecting an expansion rate of 54%. Notably, the presence of IDH1 mutation and the cumulative dose of steroids are identified as significant negative predictors of expansion efficacy. The expanded tr-TILs exhibit distinct phenotypic and molecular dysfunctional features yet show upregulated expression of progenitor/memory-like markers and polyclonal T-cell receptors. Importantly, these tr-TILs demonstrate specific antitumor reactivity against autologous tumor cells in both in vitro and in vivo xenograft models. These findings provide a compelling background for a personalized immunotherapeutic approach while tackling one of the most significant challenges in oncology.