Polyclonal expansion of functional tumor-reactive lymphocytes infiltrating glioblastoma for personalized cell therapy
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.
Authors
- Bianca Pollo (ORCID: https://orcid.org/0000-0002-5523-4256)
- Rosina Paterra (ORCID: https://orcid.org/0000-0001-9690-3500)
- Antonio Silvani (ORCID: https://orcid.org/0000-0002-4791-1042)
- Francesco Acerbi (ORCID: https://orcid.org/0000-0002-4063-3924)
- Rossella Valentino (ORCID: https://orcid.org/0000-0003-3440-8189)
- Catia Traversari (ORCID: https://orcid.org/0009-0008-8473-8286)
- Silvia Musio (ORCID: https://orcid.org/0000-0002-8051-7389)
- Paola Coluccia (ORCID: https://orcid.org/0000-0002-6539-3824)
- Francesco DiMeco (ORCID: https://orcid.org/0000-0001-6213-5793)
- Mariangela Farinotti (ORCID: https://orcid.org/0000-0003-0670-452X)
- Serena Pellegatta (ORCID: https://orcid.org/0000-0001-7804-9486)
- Domenico Aquino (ORCID: https://orcid.org/0000-0002-1289-9573)
- L Maddaloni (ORCID: https://orcid.org/0000-0003-4156-5975)
- Monica Patanè (ORCID: https://orcid.org/0000-0003-3567-9263)
- Marica Eoli (ORCID: https://orcid.org/0000-0003-4744-9377)
- Natalia Di Ianni (ORCID: https://orcid.org/0000-0003-0820-0720)
- Giacomo Baso (ORCID: https://orcid.org/0000-0002-7909-3451)
- Aldo Galluzzo
- Luca Mattei (ORCID: https://orcid.org/0000-0002-7330-502X)
- Agnese Rumolo (ORCID: https://orcid.org/0000-0002-9471-2310)
- Irene Sambruni (ORCID: https://orcid.org/0000-0002-2409-8386)
- Daniela Montagna (ORCID: https://orcid.org/0000-0002-1533-579X)
- Martina Maffezzini (ORCID: https://orcid.org/0000-0002-3527-2204)
- Manuela Zingarelli
- Arianna Berlendis (ORCID: https://orcid.org/0009-0000-3019-3315)
- F Agistri
- Manuel Facciolla
Institutions
- University of Pisa (IT)
- Johns Hopkins University (US)
- University of Milan (IT)
- University of Pavia (IT)
- Policlinico San Matteo Fondazione (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Neurological Surgery (US)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Azienda Ospedaliera Universitaria Pisana (IT)
- Politecnico di Milano (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-25
- DOI
- https://doi.org/10.1038/s41467-025-62263-2
- Citations
- 1
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- Tumori Foundation
- Universidad Pedagógica y Tecnológica de Colombia
- Associazione Italiana per la Ricerca sul Cancro
- Fondazione Italiana per la Ricerca sul Cancro