bims-mesote 2026-01-25 papers

Issue of 2026–01–25
four papers selected by
Laura Mannarino, Humanitas Research

Neoplasma. 2026 Jan 21. pii: 251018N437. [Epub ahead of print]

Prognostic value and clinical significance of tumoral PD-L1 and stromal α-SMA expression in diffuse pleural mesothelioma.

Yeqi Sun, Lan Li, Lei Cai, Jihua Yang, Jun Qian, Fajiu Wang, Lifeng Wang.

Diffuse pleural mesothelioma (PM) is a rare malignant neoplasm with an extremely poor prognosis. Prognostic assessment remains challenging, highlighting the urgent need for reliable biomarkers to guide precise and effective therapy. Programmed death ligand 1 (PD-L1) has been suggested as a predictive biomarker for PM, but existing data are limited and controversial. Although advances have been made in understanding cancer-associated fibroblasts (CAFs) within the PM tumor microenvironment, their clinical and prognostic significance remains poorly elucidated. A retrospective analysis of 51 pathologically diagnosed PM was performed. We evaluated clinicopathological factors (including tumoral PD-L1, stromal α-SMA, and Ki-67 percentage by immunohistochemistry) and analyzed their correlation with overall survival (OS) using Kaplan-Meier and multivariate Cox regression. A total of 12 potential prognostic factors were evaluated in the univariate analysis, and 6 factors were found to be significantly associated with a poor prognosis in PM patients. Multivariate analysis identified histological classification, TNM stage, and PD-L1 expression as independent prognostic factors in PM patients. Stromal α-SMA positivity, a marker of poor prognosis, was significantly correlated with male, non-epithelioid subtype, and a high Ki-67 index. Moreover, α-SMA positivity tended to show an increased likelihood of PD-L1 expression (p = 0.065). The expression of tumor PD-L1 could serve as an adverse prognostic factor for PM patients. Its potential association with tumor stromal α-SMA expression warrants further investigation, particularly in the context of unmet needs in tumor immunotherapy.

DOI: https://doi.org/10.4149/neo_2026_251018N437

Cancer Sci. 2026 Jan 20.

Cancer-Specific Antihuman Podoplanin Antibody chLpMab-2f Exerts Antitumor Effects Against Pleural Mesothelioma.

Aito Yoshida, Shinji Abe, Toshihiro Izumi, Satoshi Itakura, Keichiro Yamada, Takuya Wada, Takaaki Yamamoto, Chiemi Sato, Atsushi Mitsuhashi, Hirokazu Ogino, Seidai Sato, Tsutomu Shinohara, Masaki Hanibuchi, Mika K Kaneko, Yukinari Kato, Yasuhiko Nishioka.

Pleural mesothelioma (PM) is a malignancy with a poor prognosis owing to its resistance to chemotherapy. To develop a novel treatment for PM, podoplanin (PDPN), a transmembrane glycoprotein, has attracted significant attention because it is highly expressed in PM and is used for its diagnosis. We previously reported that NZ-12, a human chimeric antihuman PDPN antibody, exhibits antitumor effects against human PM cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Additionally, we developed a cancer-specific monoclonal antibody (CasMab) production technology and produced a mouse-human chimeric cancer-specific antihuman PDPN antibody, chLpMab-2, along with an afucosylated version, chLpMab-2f, to enhance ADCC activity. This study aimed to evaluate whether chLpMab-2f exhibits specific antitumor effects against PM in a preclinical model. We demonstrated that chLpMab-2f recognized the surface PDPN of human PM cell lines and human PM patient tissue but did not react with human normal tissues such as lung and kidney tissues. Furthermore, these antibodies exhibited ADCC and CDC activity against PDPN-positive PM cells while showing reduced toxicity toward non-malignant kidney-derived PDPN-positive cells, such as HEK-293FT. Additionally, chLpMab-2f demonstrated stronger ADCC activity through more efficient NK cell activation in comparison to chLpMab-2. Moreover, chLpMab-2f suppressed tumor progression in subcutaneously and intrathoracically transplanted human PM cells in mice. These findings suggest that PDPN-targeting immunotherapy with chLpMab-2f generated by CasMab technology could provide an effective treatment for PM with decreased toxicity toward normal tissues.

Keywords: antibody‐dependent cellular cytotoxicity; immunotherapy; mesothelioma; monoclonal antibodies; podoplanin

DOI: https://doi.org/10.1111/cas.70325

Oxf Open Immunol. 2026 ;7(1): iqaf008

Comparative analysis of malignant pleural effusion and peripheral blood reveals unique T cell signatures associated with survival in mesothelioma patients.

Nicola Principe, Kofi L P Stevens, Amber-Lee Phung, Melanie McCoy, Joel Kidman, Ali Ismail, Alistair M Cook, Abha Chopra, Mark Watson, Bruce W Robinson, Jenette Creaney, Y C Gary Lee, Jason Waithman, W Joost Lesterhuis, Richard A Lake, Anna K Nowak, Jonathan Chee, Alison M McDonnell.

The success of cancer immunotherapies has highlighted the importance of monitoring the anti-tumour T cell response. Patients with mesothelioma frequently present with a malignant pleural effusion (MPE) that is commonly drained regularly to alleviate symptoms. As MPE contains tumour cells, T cells and cytokines, it provides a unique opportunity to sample immune events at the tumour site. However, there is minimal information on how MPE T cells are distinct from those in the blood, and whether T cell phenotypes unique to each compartment correlate with survival. We characterised T cell populations of matched MPE and blood from 31 mesothelioma patients using flow cytometry and bulk T cell receptor beta (TCRβ) sequencing. MPE CD8+ and CD4+ T cells displayed increased expression of PD-1, TIGIT, LAG-3 and TIM-3 compared to blood, with co-expression of inhibitory receptors greatest on MPE CD8+ T cells with a tissue resident memory T cell phenotype (CD69+CD103+). CD8+ TCRβ repertoires displayed clonal overlap between MPE and blood, suggesting that a majority of T cells traffic between these compartments. Finally, we show that high expression of PD-1 on circulating CD4+ T cells is an independent prognostic factor for poor survival in this patient group. This work suggests that MPE T cell phenotypes differ from those in circulation, with blood-based T cell subsets more sensitive predictors of outcome in this study.

Keywords: CD8+ T cells; TCR sequencing; malignant pleural effusion; mesothelioma; tissue resident memory T cells

DOI: https://doi.org/10.1093/oxfimm/iqaf008

Thorac Cancer. 2026 Jan;17(2): e70243

Risk Factors of Hematological Toxicity of Mesothelioma Treatment-A Territory-Wide Retrospective Study.

Wang Chun Kwok, Desmond Yat Hin Yap, Isaac Sze Him Leung, James Chung Man Ho.

BACKGROUND: While chemotherapy remains the treatment of choice for mesothelioma, it carries significant toxicities, especially hematological toxicity.
METHODS: We conducted this territory-wide retrospective study in Hong Kong to investigate the prevalence and risk factors of hematological toxicity associated with mesothelioma treatment.
RESULTS: A total of 222 patients were included in the analysis. Lower baseline serum albumin level and more lines of cytotoxic chemotherapy received were risk factors for developing grade 3-4 hematological toxicity with aOR of 1.05 (95% CI, 1.02-1.09, p = 0.003) and 1.50 (95% CI, 1.03-2.19, p = 0.033) respectively. Risk factors for developing neutropenic fever included: diabetes mellitus (aOR = 9.44, 95% CI, 2.59-34.45, p < 0.001); the use of chemotherapy other than pemetrexed (aOR = 4.80, 95% CI, 1.05-21.89, p = 0.043); the presence of third-space fluid (aOR = 3.58, 95% CI, 1.16-11.05, p = 0.027), pleural effusion (aOR = 4.20, 95% CI, 1.34-13.17, p = 0.014) and pericardial effusion (aOR = 7.97, 95% CI, 1.18-53.93, p = 0.033). Number of lines of cytotoxic chemotherapy the patients received was the risk factor for pack cell transfusion with aOR of 2.35 (95% CI, 1.54-3.60, p < 0.001).
CONCLUSION: Hematological toxicities were commonly seen in the treatment course of mesothelioma. Risk factors include disease factors and treatment factors. Use of ICI could bring about hope in reducing the risk of hematological toxicities.

Keywords: hematological toxicity; mesothelioma; risk factors

DOI: https://doi.org/10.1111/1759-7714.70243