IMMU-26. Reinvigorating exhausted T cells in glioblastoma via PD1-IL2v immunocytokine therapy Article Swipe

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Ulisse Salazar , Sereina Deplazes , Valeria Nicolini , Laura Codarri Deak , Christian Klein ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1093/neuonc/noaf201.0824

Glioblastoma (GBM) remains one of the most lethal primary brain tumors, characterized by profound immunosuppression and resistance to conventional immunotherapy. A hallmark of the GBM microenvironment is the prevalence of functionally exhausted T cells, marked by sustained expression of inhibitory receptors such as PD-1 and impaired effector function. These exhausted T cells represent a major barrier to durable anti-tumor immunity and effective immunotherapeutic intervention. To address this, we explored PD1-IL2v, an engineered immunocytokine designed to selectively stimulate PD-1⁺ cells with IL-2 signaling while minimizing activation of regulatory T cells. Using both the immunogenic GL261 and the immune checkpoint-resistant SB28 murine models of GBM, we administered PD1-IL2v either systemically or directly into the tumor. Flow cytometry was employed to assess changes in tumor-infiltrating lymphocytes, with particular focus on exhaustion and effector phenotypes. Notably, local administration of PD1-IL2v, but not systemic delivery, effectively reactivated CD8⁺ T cells within the tumor microenvironment. PD1-IL2v treated mice exhibited enhanced cytokine production, increased proliferation, and restoration of cytotoxic activity in T cells. Phenotypic profiling of tumor infiltrating lymphocytes (TILs) revealed an expansion of a stem-like subset of exhausted T cells (PD-1⁺TCF1⁺), alongside the emergence of a novel, differentiated population with superior effector functions, termed “better-effector” T cells. Therapeutic intervention with PD1-IL2v led to complete tumor rejection in a subset of animals, and increased infiltration of functional T cells into the tumor core. Our findings underscore T cell exhaustion as an untapped reservoir of tumor-reactive T cells that can be therapeutically reinvigorated using PD1-IL2v. This approach not only restores anti-tumor immunity but also induces superior effector populations capable of driving tumor regression.

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Type: article
Language: en
Landing Page: https://doi.org/10.1093/neuonc/noaf201.0824
PDF: https://academic.oup.com/neuro-oncology/article-pdf/27/Supplement_5/v208/65255256/noaf201.0824.pdf
OA Status: bronze
OpenAlex ID: https://openalex.org/W4416140530

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OpenAlex ID: https://openalex.org/W4416140530

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DOI: https://doi.org/10.1093/neuonc/noaf201.0824

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Title: IMMU-26. Reinvigorating exhausted T cells in glioblastoma via PD1-IL2v immunocytokine therapy

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Type: article

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Language: en

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Publication year: 2025

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Publication date: 2025-11-01

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Authors: Ulisse Salazar, Sereina Deplazes, Valeria Nicolini, Laura Codarri Deak, Christian Klein

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Landing page: https://doi.org/10.1093/neuonc/noaf201.0824

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