bims-mesote 2025-06-01 papers

Issue of 2025–06–01
three papers selected by
Laura Mannarino, Humanitas Research

Pathol Res Pract. 2025 May 27. pii: S0344-0338(25)00241-9. [Epub ahead of print]271 156048

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

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

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.

Keywords: Chemotherapy; Immune checkpoint inhibitors (ICIs); Immunotherapy; Malignant pleural mesothelioma (MPM); Programmed death ligand 1 (PD-L1)

DOI: https://doi.org/10.1016/j.prp.2025.156048

Biomolecules. 2025 May 07. pii: 678. [Epub ahead of print]15(5):

Hyperthermic Intrathoracic Chemoperfusion and the Role of Adjunct Immunotherapy for the Treatment of Pleural Mesothelioma.

Susan Luozheng Kong, Zihan Feng, Sangmin Kim, Edra K Ha, Kero Kamel, Michael Becich, James D Luketich, Arjun Pennathur.

Pleural mesothelioma (PM) is an aggressive cancer originating from the mesothelial lining of the pleura, with a rising global incidence since the mid-20th century due to asbestos and erionite exposure. PM accounts for 80-90% of all mesothelioma cases and is histologically classified into three subtypes-epithelioid, sarcomatoid, and biphasic- with epithelioid carrying the most favorable prognosis. Despite advances in surgery, chemotherapy, radiotherapy, and immunotherapy, PM prognosis remains poor, necessitating more effective, multimodal strategies. Hyperthermic intrathoracic chemoperfusion (HITHOC) has emerged as a promising adjunct to cytoreductive surgery by delivering heated chemotherapy directly to the pleural cavity, potentially improving survival-especially in patients with epithelioid PM. Combining HITHOC with post-surgical immunotherapy represents a novel approach to enhancing both local and systemic anti-tumor responses and targeting microscopic disease and distant metastases. This review explores surgical outcomes after surgery for PM, the therapeutic synergy of HITHOC and immunotherapy, ongoing clinical trials evaluating this multimodal strategy, and its implications for future patient care.

Keywords: hyperthermic intrathoracic chemoperfusion; immunotherapy; pleural mesothelioma

DOI: https://doi.org/10.3390/biom15050678

Oncoimmunology. 2025 Dec;14(1): 2512104

Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma.

Sophie Rovers, Jonas Van Audenaerde, Ruben Verloy, Jorrit De Waele, Louize Brants, Christophe Hermans, Ho Wa Lau, Céline Merlin, Maria Möller Ribas, Peter Ponsaerts, Steven Van Laere, Filip Lardon, An Wouters, Scott A Fisher, Jan van Meerbeeck, Elly Marcq, Evelien Smits.

Pleural mesothelioma (PM) is an aggressive cancer caused by asbestos exposure, with limited treatment options and poor prognosis, highlighting the need for more effective therapies. Combining immune checkpoint blockade with anti-angiogenic therapy has shown potential in other cancers. Our study investigated the combined inhibition of PD-L1 and VEGFR2 in a mouse model of PM. Using C57BL/6 mice with subcutaneous AE17 mesothelioma tumors, we assessed the effects of anti-PD-L1 therapy with induction, concomitant, or consolidation anti-VEGFR2 treatment. Mice received intraperitoneal doses every three days for three treatments. Tumor growth, survival, tumor-infiltrating immune cells and intra-tumoral vasculature were analyzed. Results demonstrated that combining anti-PD-L1 with induction or concomitant anti-VEGFR2 significantly delayed tumor growth, improved survival, and promoted vascular maturation. Flow cytometry suggested T cell exhaustion in monotherapy groups, while no significant changes were seen with concomitant treatment. Depleting CD4+ T cells reversed the positive effects of concomitant treatment. These findings suggest that dual inhibition of PD-L1 and VEGFR2 is a promising therapeutic approach for PM, with CD4+ T cells playing a critical role in the immune response. This dual targeting of immune checkpoints and angiogenesis offers a potential new avenue for improving outcomes in PM treatment and warrants further clinical exploration.

Keywords: Anti-angiogenesis; cancer immunotherapy; combination therapy; immune checkpoint blockade; pleural mesothelioma

DOI: https://doi.org/10.1080/2162402X.2025.2512104