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LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness
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Journal Article
LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness
2024
Overview
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.
The lysine-specific histone demethylase 1 A (LSD1) can regulate cytotoxic CD8 T cell (CTL) responses and anti-tumor immunity. Here the authors show that ex vivo epigenetic reprogramming with a LSD1 inhibitor enhances cell persistence and anti-tumor activity of adoptively transferred CD8 T cells in preclinical tumor models.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/21
/ 13/31
/ 13/95
/ 14
/ 14/1
/ 38
/ 38/91
/ 64
/ 64/110
/ 64/60
/ Animals
/ B7-H1 Antigen - antagonists & inhibitors
/ CD8-Positive T-Lymphocytes - immunology
/ Female
/ Histone Demethylases - antagonists & inhibitors
/ Histone Demethylases - metabolism
/ Histones
/ Humanities and Social Sciences
/ Humans
/ Immunity
/ Immunotherapy, Adoptive - methods
/ Lysine
/ Melanoma
/ Melanoma, Experimental - immunology
/ Melanoma, Experimental - therapy
/ Mice
/ Science
/ T-Lymphocytes, Cytotoxic - drug effects
/ T-Lymphocytes, Cytotoxic - immunology
/ Therapy
/ Tumors
