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

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.

Conclusions: 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.