bims-mesote 2022-10-09 papers

Issue of 2022–10–09
four papers selected by
Laura Mannarino, Humanitas Research

Interact Cardiovasc Thorac Surg. 2022 Oct 07. pii: ivac255. [Epub ahead of print]

Kohei Ando, Takao Morohoshi, Yukio Tsuura, Munetaka Masuda.

Although the diagnosis of malignant pleural mesothelioma at an in situ stage was traditionally challenging, it is now possible owing to advances in molecular biological methods such as P16 fluorescence in situ hybridization or BRCA1-associated protein 1 immunohistochemistry. Here, we report the first case, to our knowledge, of total parietal pleurectomy for mesothelioma in situ. Future follow-up and accumulation of cases are necessary to determine whether total parietal pleurectomy could be applied as a treatment for mesothelioma in situ or not.

Keywords: in situ; malignant pleural mesothelioma; pleurectomy

DOI: https://doi.org/10.1093/icvts/ivac255

Int J Radiat Oncol Biol Phys. 2022 Oct 03. pii: S0360-3016(22)03414-9. [Epub ahead of print]

Emerging role of immunomonitoring to predict the clinical outcome of patient with Malignant Pleural Mesothelioma treated with radical radiation therapy.

Michela Cangemi, Marcella Montico, Marco Trovo, Emilio Minatel, Emanuela Di Gregorio, Giuseppe Corona, Fabiana Giordari, Elisa Comaro, Francesca Colizzi, Lorena Baboçi, Agostino Steffan, Alberto Revelant, Elena Muraro.

PURPOSE: The present paper aimed at evaluating the baseline immune profile and the immunomodulating effects of radical hemithoracic radiotherapy (RT) in patients affected by Malignant Pleural Mesothelioma (MPM) in order to identify potential predictive biomarkers of therapy response, toxicity development, and eligibility for further immunotherapeutic treatments.
METHODS AND MATERIALS: Blood samples were collected from 55 MPM patients, enrolled in a phase III trial comparing radical hemithoracic RT (interventional arm, n=28) with local palliative RT (control arm, n=27). Immunomonitoring was performed before RT, at the end of treatment, and 1 month after therapy, characterizing NK cells, B and T lymphocytes, activated CD4 and CD8 T cells, IFN-γ- and TNF-α- producing T helper (Th) 1 cells, regulatory T cells, Th17 and Th22 lymphocytes, through flow cytometry. Serum levels of Interleukin (IL)-6, IL-8, IL-10, and mesothelin were quantified through ELISA assays at the same time points. Variations in the immune parameters were investigated by Friedman test and Wilcoxon signed-rank post-hoc test with Bonferroni correction for multiple testing, while the prognostic impact of immune biomarkers was evaluated through Kaplan-Meier method and Spearman's correlation analysis.
RESULTS: Major immune variations were noticed after radical RT compared to palliative treatment, in particular an improvement in activated T cells, and in IFN-γ-producing Th1 cells, after RT. In the interventional arm, baseline high levels of Th22 and IL-10, and an increase in T cells were associated with an improved survival. Whereas a fold increase in serum mesothelin correlated with the development of severe toxicity. An improvement of immunosuppressive regulatory T cells was observed in both arms of treatment.
CONCLUSION: The immunomonitoring performed in MPM patients revealed potential prognostic biomarkers for radical hemithoracic RT treatment, and identify specific immune signatures induced by RT-immunomodulation, which could suggest a synergistic effect with an immunotherapeutic treatment.

DOI: https://doi.org/10.1016/j.ijrobp.2022.09.079

Sci Rep. 2022 Oct 04. 12(1): 16583

Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration.

Kui Fan, Chuan-Long Zhang, Bo-Hui Zhang, Meng-Qi Gao, Yun-Chuan Sun.

Mesothelioma lies one of the most malignant tumors, in which the identification of the corresponding biomarkers is extremely critical. This study aims to investigate the prognostic value of enhancer homolog 2 (EZH2) mRNA expression in mesothelioma patients accompanied with its immune infiltration analysis. Gene expression, clinical information and enrichment analysis were obtained based on the Cancer Genome Atlas (TCGA), the immune infiltration analysis and bioinformatics analysis were performed. Clinical information and gene expression were obtained from 86 patients with mesothelioma based on TCGA database. Survival analysis, GSEA enrichment analysis, and immune infiltration analysis of EZH2 expression were carried out using R (version 3.6.3) (statistical analysis and visualization). The correlation of EZH2 expression with immune cell infiltration in mesothelioma was analyzed according to the TIMER database (Fig. https://cistrome.shinyapps.io/timer/ ). A univariate and multivariate analysis of general data obtained from the TCGA database was performed, involving age, gender, stage, pathological type, and whether they had received radiotherapy, the results indicated the association of high expression of EZH2 with poor prognosis in mesothelioma patients, with the worse prognosis in the High group (HR = 2.75, 95% CI 1.68-4.52, P < 0.010). Moreover, ROC curves showed that EZH2 expression predicted 1-year survival with an AUC of 0.740, 2-year survival with an AUC of 0.756, and 3-year survival with an AUC of 0.692, suggesting a robust predictive effect of EZH2 expression on prognosis. KEGG pathway analysis indicated five pathways showing the strongest positive correlation with EZH2 expression: cell cycle, DNA replication, Cell adhesion molecules cams, Primary immuno deficiency, Tsate transduction, and five pathways showing the strongest negative correlation with EZH2 expression: Glycolysis gluconeogenesis, Drug metabolism, cytochrome P450, retinol metabolism, fatty acid metabolism ribosome. We investigated the correlation between EZH2 expression and the level of immune infiltration in mesothelioma tissues. The results indicated that EZH2 expression played a critical role in immune infiltration, of which the high expression was correlated with the reduced number of NK cells, Mast cells, and Th17 cells. Moreover, mesothelioma patients with high EZH2 expression differ from those with low EZH2 expression in their tumor immune microenvironment. EZH2, as a new prognostic biomarker for mesothelioma, contributes to elucidating how changes in the immune environment promote the development of mesothelioma. Further analysis, EZH2 may serve as a biological test to predict the prognosis of mesothelioma.

DOI: https://doi.org/10.1038/s41598-022-21005-w

J Thorac Oncol. 2022 Sep 29. pii: S1556-0864(22)01695-1. [Epub ahead of print]

Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective from the IASLC Pathology Committee.

IASLC Pathology Committee

Immunotherapy including immune checkpoint inhibitors (ICIs) has become the backbone of treatment for the majority of lung cancers with advanced or metastatic disease. In addition, they have increasingly been used for early-stage tumors in neoadjuvant and adjuvant settings. Unfortunately, however, only a subset of patients experiences meaningful response to ICIs. While PD-L1 protein expression by immunohistochemistry (IHC) has played a role as the principle predictive biomarker for immunotherapy, its performance may not be optimal, and it suffers multiple practical issues with different companion diagnostic assays approved. Similarly, tumor mutation burden (TMB) has multiple technical issues as a predictive biomarker for ICIs. Now, ongoing research on tumor and host immune-specific factors has identified immunotherapy biomarkers that may provide better response and prognosis prediction, in particular in a multimodal approach. This review by the IASLC Pathology Committee provides an overview of various immunotherapy biomarkers including updated data on PD-L1 IHC and TMB, and assesssments of neoantigens, genetic and epigenetic signatures, immune microenvironment by IHC and transcriptomics, as well as microbiome and pathological response to neoadjuvant immunotherapies. The aim of this review is to underline the efficacy of new individual or combined predictive biomarkers beyond PD-L1 IHC and TMB.

DOI: https://doi.org/10.1016/j.jtho.2022.09.109