EXTH-43. Ara-C suppresses H3 K27-altered spinal cord diffuse midline glioma growth and enhances immune checkpoint blockade sensitivity
Year: 2025
Type: conference-abstract
Abstract: H3 K27-altered spinal cord diffuse midline glioma (H3-SCDMG) represents a challenging malignancy with limited treatment options and experiment models. This study aimed to investigate novel therapeutic strategies for H3-SCDMG by leveraging the tumor’s biological characteristics and newly established experiment models. Immunohistochemistry analysis of 73 clinical samples revealed heightened cell proliferation in H3-SCDMG compared to H3-wildtype-SCDMG, setting the stage for further exploration. Screening multiple candidate drugs in H3 K27M-mutant cell models, with enhanced cell proliferation, identified Cytarabine (Ara-C) as a potent contender, showing superior efficacy in inhibiting cell proliferation. Subsequent experimentation with newly established patient-derived cells and patient-derived xenograft models specifically to H3-SCDMG demonstrated Ara-C’s ability to suppress tumor growth through DNA damage induction, cell cycle arrest, and apoptosis. An investigator-initiated clinical trial involving four patients highlighted notable benefits in three individuals treated with Ara-C. Additionally, a subset of cells exhibited senescence post-Ara-C treatment, attracting immune cells through the senescence-associated secretory phenotype (SASP) while evading immune clearance via serval immune checkpoint ligands upregulation. Combining Ara-C with dual PD-1 and TIGIT blockade emerged as a promising strategy to disrupt immune evasion by senescent cells, potentially enhancing antitumor immune responses. This study positions Ara-C as a promising therapeutic option for H3-SCDMG, demonstrating its efficacy in impeding proliferation, modulating tumor immune infiltration, and synergizing with immune checkpoint inhibitors for enhanced antitumor effects. These findings offer valuable insights for advancing treatment approaches in H3-SCDMG management.
Source: Neuro-Oncology
Authors: Ruichao Chai, Bo Pang, Yilin Wu, Tao Jiang, Yongzhi Wang
Institution: Beijing Institute of Neurosurgery
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416140183
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