Cisplatin potentiates PD-L1 expression more robustly than pemetrexed in malignant pleural mesothelioma: Temporal dynamics revealed by cellular and xenograft analyses

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-05-27 DOI:10.1016/j.prp.2025.156048

Zhenghua Zhang , Wenjun Gao , Feng Yuan , Yubin Hu , Xiaoyu Tuo , Liangping Luo , Xiaonan Tang , Shasha Shen , Yang Tian , Dan Han

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引用次数: 0

Abstract

Objective

Chemotherapy may modulate PD-L1 expression in malignant pleural mesothelioma (MPM), influencing immune checkpoint inhibitor (ICI) efficacy. We compared cisplatin (CDDP) and pemetrexed (PEM) on PD-L1 dynamics in MPM.

Methods

H226 (epithelial) and MSTO-211H (biphasic) cells were treated with CDDP/PEM for 12–48 h, with apoptosis analyzed by flow cytometry and PD-L1 by Western blot. Xenograft models (CDDP/PEM-treated mice) assessed tumor growth and PD-L1 via immunohistochemistry.

Results

Both drugs inhibited cell growth and induced apoptosis (CDDP > PEM, P < 0.05). Baseline PD-L1 was higher in MSTO-211H vs. H226 (P < 0.05). Chemotherapy upregulated PD-L1, peaking at 48 h (CDDP > PEM, P < 0.05). In xenografts, MSTO-211H tumors showed faster growth and higher PD-L1 (P < 0.05), further amplified by CDDP during progression.

Conclusion

CDDP robustly potentiates PD-L1 in MPM, especially in biphasic subtypes. Temporal PD-L1 dynamics suggest chemotherapy-ICI synergy may depend on drug selection and treatment timing.

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在恶性胸膜间皮瘤中，顺铂比培美曲塞更能增强PD-L1的表达：细胞和异种移植物分析揭示的时间动态

目的化疗可调节恶性胸膜间皮瘤（MPM）组织中PD-L1的表达，影响免疫检查点抑制剂（ICI）的疗效。我们比较顺铂（CDDP）和培美曲塞（PEM）对MPM患者PD-L1动态的影响。方法用CDDP/PEM处理sh226（上皮细胞）和MSTO-211H（双相细胞）12-48 h，流式细胞术和Western blot检测细胞凋亡情况。异种移植模型（CDDP/ pem处理小鼠）通过免疫组织化学评估肿瘤生长和PD-L1。结果两种药物均抑制细胞生长，诱导细胞凋亡(CDDP >；PEM, P & lt; 0.05)。MSTO-211H组PD-L1基线高于H226组（P <； 0.05）。化疗上调PD-L1，在48 h (CDDP >；PEM, P & lt; 0.05)。在异种移植物中，MSTO-211H肿瘤表现出更快的生长和更高的PD-L1 (P <； 0.05)，在进展过程中被CDDP进一步扩增。结论cddp在MPM中增强PD-L1，特别是在双相亚型中。时间PD-L1动力学提示化疗- ici协同作用可能取决于药物选择和治疗时间。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.