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

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

PROVIDER: PRJNA1138703 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29914823_1.fastq.gz	Fastqsanger.gz
	SRR29914823_2.fastq.gz	Fastqsanger.gz
	SRR29914824_1.fastq.gz	Fastqsanger.gz
	SRR29914824_2.fastq.gz	Fastqsanger.gz
	SRR29914825_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

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

Project description: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.

2024-07-23 | GSE272770 | GEO

LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8<sup>+</sup> T cell responsiveness.

Project description: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.

| S-EPMC11349769 | biostudies-literature

Enhancing tumor response to adoptive T cell therapy by targeting PHD2/3 in CD8 T cells

Project description:Enhancing tumor response to adoptive T cell therapy by targeting PHD2/3 in CD8 T cells

| PRJNA1130998 | ENA

Adoptive cell therapy [Fig.4]

Project description:Adoptive cell therapy [Fig.4]

| PRJNA821483 | ENA

LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma

Project description:Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that lacks actionable mutations, which could be utilized for targeted therapies. Epigenetic regulators governing cell identity may represent unexplored therapeutic entry points. Here, we targeted epigenetic regulators in a pharmacological screen and discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. We show that LSD1 inhibition in MCC disrupts the LSD1-CoREST complex leading to displacement and degradation of HMG20B (BRAF35), a poorly characterized complex member that is essential for MCC proliferation. Inhibition of LSD1 causes derepression of transcriptional master regulators of the neuronal lineage, activates a gene expression signature resembling normal Merkel cells, and induces cell cycle arrest and cell death. Our study unveils the importance of LSD1 for proliferation and maintaining cell identity in MCC. There is growing evidence that cancer cells exploit cellular plasticity and dedifferentiation programs to evade destruction by the immune system. The combination of LSD1 inhibitors with checkpoint inhibitors may thus represent a promising treatment strategy for MCC patients.

2020-11-03 | PXD020590 | Pride

Adoptive cell therapy across cancer diagnoses

Project description:Primary objectives: The main objective is to determine the feasibility and safety of adoptive cell therapy in combination with checkpoint inhibition across different metastatic solid cancers. Primary endpoints: Toxicity: Registration of all AEs and unexpected events in relation to the treatment will be done in accordance with the common terminology criteria for adverse events (CTCAE) criteria as described in appendix 3.

| 2537065 | ecrin-mdr-crc

LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade

Project description:Chromatin regulators play a broad role in regulating gene expression, and when gone awry, can lead to cancer. Here we demonstrate that ablation of the histone demethylase LSD1 in cancer cells increases repetitive element expression, including ERVs, and decreases expression of RNA-induced silencing complex (RISC) components. Significantly, this leads to dsRNA stress and activation of type 1 interferon, which stimulates anti-tumor T cell immunity and restrains tumor growth. Furthermore, LSD1 depletion enhances tumor immunogenicity and T cell infiltration in poorly immunogenic tumors, and elicits significant responses of checkpoint blockade-refractory mouse melanoma to anti-PD-1 therapy. Consistently, TCGA data analysis shows an inverse correlation between LSD1 expression and CD8+ T cell infiltration in various human cancers. Our study identifies LSD1 as a potent inhibitor of anti-tumor immunity and responsiveness to immunotherapy, and suggests LSD1 inhibition combined with PD-(L)1 blockade as a novel cancer treatment strategy.

2018-06-21 | GSE112230 | GEO

Small extracellular vesicles-delivered LSD1 promotes gastric cancer cell stemness

Project description:Although there are plenty of researches about nucleic acid in small extracellular vesicles (sEVs), properties of proteins identified as sEVs’ cargos and the mechanism of their action in recipient cell are poorly understood. Here, we show that lysine specific demethylase 1 (LSD1), the first identified histone demethylase in 2004, existed in the cell cultured medium of gastric cancer cells. Further investigation confirmed the presence of LSD1 in sEVs from gastric cancer cells and gastric cancer patient plasma, which is the first identified histone demethylase in sEVs. By shuttling from donor cells to recipient gastric cancer cells, sEVs-delivered LSD1 promoted the cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2 and CD44, and suppressed the oxaliplatin response of the recipient cells in vitro and in vivo, while LSD1 depleted sEVs failed to suppress the oxaliplatin response. Collectively, our findings give an evidence for LSD1 as a sEVs protein to promote stemness and suppress oxaliplatin response for the first time and constitute a future avenue to predict oxaliplatin response in gastric cancer clinically.

2021-07-30 | PXD021511 | Pride

Small extracellular vesicles-delivered LSD1 promotes gastric cancer cell stemness

2021-12-22 | PXD020223 | Pride

LSD1 complexes - Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Project description:Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue. Lsd1 protein complexes were purified from mouse adipose tissue and analyzed by label-free LC-MS/MS. Mice were kept under different conditions prior complex isolation.

2017-01-03 | PXD004745 | Pride

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