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

Animals Histone Demethylases / metabolism Immunotherapy, Adoptive / methods Mice Female CD8-Positive T-Lymphocytes / immunology Mice, Inbred C57BL Melanoma, Experimental / immunology Cell Line, Tumor B7-H1 Antigen / antagonists & inhibitors T-Lymphocytes, Cytotoxic / immunology Humans Melanoma / immunology

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
27 Aug 2024

Historique:

received: 14 11 2023

accepted: 09 08 2024

medline: 28 8 2024

pubmed: 28 8 2024

entrez: 27 8 2024

Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-51500-9 PMID: 39191730

pubmed: 39191730

doi: 10.1038/s41467-024-51500-9

pii: 10.1038/s41467-024-51500-9

doi:

Substances chimiques

Histone Demethylases EC 1.14.11.-

KDM1a protein, mouse EC 1.14.11.-

B7-H1 Antigen 0

Cd274 protein, mouse 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

7366

Subventions

Organisme : Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)

ID : 21474

Informations de copyright

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