LSD1 抑制通过增强 CD8 T 细胞反应性来提高过继性 T 细胞疗法的疗效。
LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness.
发表日期：2024 Aug 27
作者：
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 Preto, Alberto Bigogno, Eleonora Sala, Matteo Iannacone, Ciro Mercurio, Luca Gattinoni, Ignazio Caruana, Mirela Kuka, Luigi Nezi, Saverio Minucci, Teresa Manzo
来源：
Epigenetics & Chromatin
摘要：
赖氨酸特异性组蛋白去甲基酶 1 A (LSD1) 参与抗肿瘤免疫；然而，它在塑造 CD8 T 细胞 (CTL) 分化和功能方面的作用在很大程度上仍未被探索。在这里，我们表明，在过继性 T 细胞疗法 (ACT) 的背景下，CTL 中 LSD1 (LSD1i) 的药理抑制会引起表型和功能改变，从而在雌性小鼠的临床前模型中产生强大的抗肿瘤免疫力。此外，抗 PDL1 治疗与基于 LSD1i 的 ACT 相结合可以根除肿瘤，并在黑色素瘤模型中实现长期无瘤生存，补充了单独免疫或表观遗传治疗的有限疗效。总的来说，这些结果表明 LSD1 调节可改善 ACT 和抗 PDL1 疗法产生的抗肿瘤反应，为其临床评估提供基础。© 2024。作者。
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.© 2024. The Author(s).