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LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness

Author

Listed:
  • Isabella Pallavicini

    (Department of Experimental Oncology)

  • Teresa Maria Frasconi

    (Department of Experimental Oncology)

  • Carlotta Catozzi

    (Department of Experimental Oncology)

  • Elena Ceccacci

    (Department of Experimental Oncology)

  • Silvia Tiberti

    (Department of Experimental Oncology)

  • Dorothee Haas

    (Oncology and Stem Cell Transplantation Unit- University Hospital of Würzburg)

  • Jule Samson

    (Oncology and Stem Cell Transplantation Unit- University Hospital of Würzburg)

  • Christoph Heuser-Loy

    (Leibniz Institute for Immunotherapy)

  • Carina B. Nava Lauson

    (Department of Experimental Oncology)

  • Marta Mangione

    (Department of Experimental Oncology)

  • Elisa Preto

    (Department of Experimental Oncology)

  • Alberto Bigogno

    (Department of Experimental Oncology)

  • Eleonora Sala

    (Vita-Salute San Raffaele University
    IRCCS San Raffaele Scientific Institute)

  • Matteo Iannacone

    (Vita-Salute San Raffaele University
    IRCCS San Raffaele Scientific Institute)

  • Ciro Mercurio

    (the FIRC Institute of Molecular Oncology IFOM)

  • Luca Gattinoni

    (Leibniz Institute for Immunotherapy
    University of Regensburg)

  • Ignazio Caruana

    (Oncology and Stem Cell Transplantation Unit- University Hospital of Würzburg)

  • Mirela Kuka

    (Vita-Salute San Raffaele University
    IRCCS San Raffaele Scientific Institute)

  • Luigi Nezi

    (Department of Experimental Oncology)

  • Saverio Minucci

    (Department of Experimental Oncology
    Department of Oncology and Hemato-Oncology)

  • Teresa Manzo

    (Department of Experimental Oncology
    University of Turin)

Abstract

The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation.

Suggested Citation

  • Isabella Pallavicini & Teresa Maria Frasconi & Carlotta Catozzi & Elena Ceccacci & Silvia Tiberti & Dorothee Haas & Jule Samson & Christoph Heuser-Loy & Carina B. Nava Lauson & Marta Mangione & Elisa , 2024. "LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51500-9
    DOI: 10.1038/s41467-024-51500-9
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    References listed on IDEAS

    as
    1. Fengqi Qiu & Peishan Jiang & Guiheng Zhang & Jie An & Kexin Ruan & Xiaowen Lyu & Jianya Zhou & Wanqiang Sheng, 2024. "Priming with LSD1 inhibitors promotes the persistence and antitumor effect of adoptively transferred T cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. N. Jacquelot & M. P. Roberti & D. P. Enot & S. Rusakiewicz & N. Ternès & S. Jegou & D. M. Woods & A. L. Sodré & M. Hansen & Y. Meirow & M. Sade-Feldman & A. Burra & S. S. Kwek & C. Flament & M. Messao, 2017. "Predictors of responses to immune checkpoint blockade in advanced melanoma," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

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