LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness
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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.
Recommended citation: Pallavicini I, Frasconi TM, Catozzi C, Ceccaci E, Tiberti S, Haas D, Samson J, Heuser-Loy C, Nava Lauson CB, Mangione M, Preto E, Bigogno A, Sala E, Iannacone M, Mercurio C, Gattinoni L, Caruana I, Kuka M, Nezi L, Minucci S, Manzo T. Nat Commun. Aug 27, 2024 (15): 7366
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