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

GSE272770 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2024/07/23 Platform GPL24247
Summary
The lysine-specific histonedemethylase1A(LSD1) has been described to play a role in antitumor immunity; however, the role of LSD1 in shaping CD8+ T cell (CTL) differentiation and function is not understood. Here, we showed that pharmacological inhibition of LSD1 (LSD1i) in CTL elicited phenotypic and functional alterations of the CTL that led to robust antitumor immunity in the context of adoptive T cell therapy (ACT). In addition, the combination of anti-PDL1 therapy with LSD1i-based ACT resulted in a complete tumor eradication and long-lasting tumor-free survival. This study demonstrated that LSD1i together with anti-PDL1 therapy complement each other’s deficiencies and produce a better tumor response in a melanoma model, in which both immune and epigenetic therapy alone have shown limited efficacy. Collectively, these results set the translational potential of modulating LSD1 to improve antitumoral responses generated by ACT and anti-PDL1 therapy, which provide a strong rationale for a combination trial of LSD1i and immunotherapy.
Published in
LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8(+) T cell responsiveness
Pallavicini I, Frasconi TM, Catozzi C et al. · Nature communications 2024 · PMID 39191730 · doi:10.1038/s41467-024-51500-9
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Also filed as BioProject PRJNA1138703 and SRA study SRP521365. Searching any of these in the dataset finder brings you back here.

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