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Frontiers in Medical Science Research, 2025, 7(4); doi: 10.25236/FMSR.2025.070408.

Mechanism Study of the Effect of GSPT1 Inhibitor MRT-2359 on Immune Escape in Non-Small Cell Lung Cancer

Author(s)

Shanle Zhou1, Jianxin Lyu2

Corresponding Author:
Jianxin Lyu
Affiliation(s)

1College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China

2Key Laboratory of Laboratory Medicine, Ministry of Education, College of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Abstract

This study is dedicated to investigating the effects of the GSPT1 inhibitor MRT-2359 on the functional modulation of immune cells in the context of non-small cell lung carcinoma and to elucidate the underlying mechanisms. Accumulating evidence has highlighted the aberrant upregulation of eRF3a/GSPT1 across a spectrum of malignancies, positioning GSPT1 as a highly promising target for therapeutic intervention. Our findings demonstrate that MRT-2359 efficaciously induces the degradation of GSPT1 within NSCLC cells. Utilizing RNA sequencing (RNA-seq) and other advanced molecular techniques, we have postulated that MRT-2359 modulates the expression of CD276, thereby suppressing the tumor immune evasion phenotype of NSCLC cells. In vivo studies corroborate the tumor-suppressive effects of MRT-2359 in murine models, with immunohistochemical analyses revealing a significant reduction in GSPT1 and CD276 within tumor tissues. Concurrently, an enhanced infiltration of granzyme B (GZMB)-positive cells was observed. These collective findings provide reference value for MRT-2359 advancement towards clinical application.

Keywords

GSPT1, MRT-2359, CD276, Non-Small Cell Lung Cancer, Immune Escape

Cite This Paper

Shanle Zhou, Jianxin Lyu. Mechanism Study of the Effect of GSPT1 Inhibitor MRT-2359 on Immune Escape in Non-Small Cell Lung Cancer. Frontiers in Medical Science Research (2025), Vol. 7, Issue 4: 63-71. https://doi.org/10.25236/FMSR.2025.070408.

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