bims-mesote 2024-05-05 papers

Issue of 2024–05–05
six papers selected by
Laura Mannarino, Humanitas Research

JTCVS Open. 2024 Apr;18 324-344

Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.

Christophe Gattlen, Kirby R Frank, Damien N Marie, Aurélien Trompette, Louis-Emmanuel Chriqui, Yameng Hao, Etienne Abdelnour, Michel Gonzalez, Thorsten Krueger, Paul J Dyson, Sviatlana Siankevich, Christophe von Garnier, Niki D J Ubags, Sabrina Cavin, Jean Y Perentes.

Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma.
Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals.
Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma.
Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Keywords: antitumor immunity; malignant pleural mesothelioma; microbiome; microbiome modulator; prebiotic

DOI: https://doi.org/10.1016/j.xjon.2024.02.007

Eur J Histochem. 2024 May 02. 68(2):

Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report.

Claudia Lombardo, Grazia Maugeri, Agata Grazia D'Amico, Giuseppe Broggi, Rosario Caltabiano, Veronica Filetti, Serena Matera, Velia D'Agata, Carla Loreto.

Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.

DOI: https://doi.org/10.4081/ejh.2024.3994

Biomed Pharmacother. 2024 Apr 30. pii: S0753-3322(24)00546-8. [Epub ahead of print]175 116662

DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.

Barbara Nuvoli, Andrea Sacconi, Grazia Bottillo, Francesca Sciarra, Roberta Libener, Antonio Maconi, Mariantonia Carosi, Giorgio Piperno, Eliuccia Mastropasqua, Maria Papale, Emanuela Camera, Rossella Galati.

17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.

Keywords: 17-β-estradiol; Androstenedione; Asbestos; DHEA-S; Malignant pleural mesothelioma; UHPLC-MS/MS, Biomarker

DOI: https://doi.org/10.1016/j.biopha.2024.116662

Front Oncol. 2024 ;14 1378530

Pathological complete response in a patient with pleural mesothelioma treated with immunotherapy: a case report.

Eleonora Faccioli, Federica Grosso, Andrea Dell'Amore, Sara Delfanti, Giovanni Zambello, Luigi Cerbone, Gianluca Canu, Antonina De Angelis, Viola Sambataro, Federica Pezzuto, Paola Barbieri, Giulia Pasello, Fiorella Calabrese, Federico Rea.

The role of immunotherapy in the multimodal treatment for pleural mesothelioma (PM) is still under investigation, particularly in the preoperative setting. Pathological complete response (pCR) has been previously described after chemotherapy and immunotherapy; however, there is no prior experience reported with immunotherapy alone before surgery. We report the case of a 58-year-old male with biphasic PM treated with immunotherapy, resulting in a major clinical partial response. Following a multidisciplinary evaluation between thoracic surgeons, medical oncologists, pathologists, radiologists and radiation oncologists, the patient underwent surgery with radical intent through a right extended pleurectomy/decortication (eP/D). Histopathological examination of the specimen confirmed a pathological Complete Response (pCR). This case supports the feasibility and potential efficacy of combining preoperative immunotherapy with surgery in the management of advanced PM.

Keywords: immunotherapy; multimodal treatment; pathological complete response; pleural mesothelioma; surgery

DOI: https://doi.org/10.3389/fonc.2024.1378530

Lung Cancer. 2024 Apr 24. pii: S0169-5002(24)00336-2. [Epub ahead of print]192 107802

Combination of calretinin, MALAT1, and GAS5 as a potential prognostic biomarker to predict disease progression in surgically treated mesothelioma patients.

Laura V Klotz, Swaantje Casjens, Georg Johnen, Dirk Taeger, Alexander Brik, Florian Eichhorn, Laura Förster, Nina Kaiser, Thomas Muley, Christa Stolp, Marc Schneider, Jan Gleichenhagen, Thomas Brüning, Hauke Winter, Martin Eichhorn, Daniel G Weber.

BACKGROUND: The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival.
METHODS: Between 03/2014 and 08/2022, preoperative blood samples were collected from 76 patients with epithelioid pleural mesothelioma who underwent cytoreductive surgery as part of a multimodal treatment approach. Identification of potential biomarkers was performed by determination of mesothelin and calretinin, as well as specific long non-coding RNAs and microRNAs. Receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression were used to assess the association between biomarker concentrations and patient recurrence status and survival.
RESULTS: MALAT1, GAS5, and calretinin showed statistically significant increased biomarker levels in patients with recurrence in contrast to recurrence-free patients after surgical treatment (p < 0.0001, p = 0.0190, and p = 0.0068, respectively). The combination of the three biomarkers resulted in a sensitivity of 68 % and a specificity of 89 %.
CONCLUSION: MALAT1, GAS5, and calretinin could be potential biomarkers for the prediction of tumor recurrence, improving the benefit from multimodal treatment including cytoreductive surgery.

Keywords: Biomarker; Calretinin; Cytoreductive surgery; Decortication; GAS5; MALAT1; Mesothelioma; Thoracic surgery; Tumor recurrence

DOI: https://doi.org/10.1016/j.lungcan.2024.107802