bims-mesote Biomed News
on Mesothelioma
Issue of 2024–12–22
seven papers selected by
Laura Mannarino, Humanitas Research



  1. Front Chem. 2024 ;12 1508912
       Objectives: Immune checkpoint inhibitors (ICIs) have demonstrated potential in inhibiting the growth of malignant pleural mesothelioma (MPM), and their efficacy is associated with the expression of programmed death-ligand 1(PD-L1). This study evaluated a PD-L1-targeted nanoprobe for detecting PD-L1 expression in a nude mouse model of malignant pleural mesothelioma (MPM).
    Methods: A PD-L1-binding peptide (WL-12) was conjugated with superparamagnetic iron oxide nanoparticles (SPIONs) to create the nanoprobe WL-12@Fe₃O₄. The nanoprobe's stability, biotoxicity, targeting ability, and in vivo magnetic resonance (MR) imaging effects were assessed and compared to non-targeted Fe₃O₄ nanoparticles. ΔT2 values and PD-L1 expression were measured in H226 and MSTO-211H tumor tissues over 4 weeks to analyze correlations.
    Results: The WL-12@Fe₃O₄ nanoprobe demonstrated uniform distribution and a spherical shape, with a larger size (43.82 nm) and lower surface potential (-9.34 ± 0.54 mV) compared to Fe₃O₄ (32.67 nm, -20.20 ± 0.88 mV, P < 0.05). The XPS and FT-IR analysis results indicate the successful coupling of WL-12 with Fe3O4. It was well dispersed in serum and saline and showed no cytotoxicity or organ damage in vivo. The probe selectively accumulated in PD-L1-expressing MPM cells, especially MSTO-211H, and exhibited significantly higher uptake in high PD-L1-expressing H460 cells (930.22 ± 11.75 ng/mL) compared to low PD-L1-expressing A549 cells (254.89 ± 17.33 ng/mL, P < 0.05). Tumor iron levels in the WL-12@Fe₃O₄ group were significantly elevated (141.02 ± 17.33 μg/g) compared to controls (36.43 ± 3.56 μg/g, P < 0.05), with no significant differences in other organs (P > 0.05). The T2 values of H226 and MSTO-211H tumors decreased after probe injection, with ΔT2 values significantly higher in the targeted group than the nontargeted group (P < 0.05). ΔT2 values increased over 4 weeks, correlating strongly with PD-L1 expression (P < 0.05).
    Conclusion: The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.
    Keywords:  immunotherapy; magnetic resonance imaging (MRI); malignant pleural mesothelioma (MPM); nanoprobe; programmed death ligand 1 (PD-L1)
    DOI:  https://doi.org/10.3389/fchem.2024.1508912
  2. Front Immunol. 2024 ;15 1480183
       Background: Pleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.
    Patients and methods: Patients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Serum cytokine levels were measured by Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay. Correlations between cytokine levels and irAEs were analyzed by generalized linear mixed models to identify potential diagnostic and predictive biomarkers.
    Results: Higher levels of MIG, eotaxin, MIP-1α, IP-10, TNF-α, MIP-1β, IL-4, MIF, IL-16, IL-2RA, SCGF.β and PDFG-BB at baseline are associated with increased risk of developing one or more irAEs. In particular, higher baseline levels of MIG are positively associated with thyroiditis and hypophysitis, and elevated levels of IP-10 and MIG to dermatitis. During the course of treatment, higher levels of MIG, eotaxin, MIF, TNF-α, MIP-1β, IL-4 and IL-16 are associated with an ongoing irAE. We found both predictive and diagnostic value of MIF with fatigue and of eotaxin with both colitis and pneumonitis. Higher levels of CTACK is associated with a lower risk of developing hepatitis, both before and after treatment.
    Conclusions: Elevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.
    Keywords:  biomarkers; checkpoint inhibition blockade; cytokines; immunotherapy; pleural mesothelioma
    DOI:  https://doi.org/10.3389/fimmu.2024.1480183
  3. J Clin Med. 2024 Dec 02. pii: 7322. [Epub ahead of print]13(23):
      Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1-25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13-0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64-15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1-25.4) vs. 31.3 (17.4-95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.
    Keywords:  BAP-1; ILK; PD-L1; multimodality treatment; pleural mesothelioma; prognostic biomarkers
    DOI:  https://doi.org/10.3390/jcm13237322
  4. J Thorac Dis. 2024 Nov 30. 16(11): 8133-8141
       Background: Malignant pleural mesothelioma (MPM) is primarily treated with a combination therapy based on lung pleurectomy in the early stage or pemetrexed combined with platinum-based chemotherapy in the late stage. However, these standard therapies do not significantly improve survival and are associated with significant adverse reactions.
    Case Description: In February 2017, a 63-year-old male patient was admitted to Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University coughing for 1 month and experienced chest tightness and chest pain for 2 days. After admission, the patient underwent thoracic puncture drainage and was diagnosed with stage IIIb (c-T4NxM0) MPM. The patient subsequently underwent left pleural biopsy under single-port thoracoscopy, followed by cytoreductive surgery plus hyperthermic intrathoracic chemotherapy as a local treatment for controlling pleural effusion. At a postoperative follow-up in October 2017, we found that he had recurrent MPM with multiple nodules on the left pleura. Despite this, the patient declined further antitumor treatment. In April 2020, the patient was readmitted to The Third Affiliated Hospital of Chongqing Medical University for left-sided chest pain and was observed to have an enlarged tumor in the left pleural according to further imaging examination. Fortunately, no further pleural effusion has been observed since then. Subsequently, the patient was administered a combination of immunotherapy and cisplatin-pemetrexed chemotherapy as systemic therapy for six cycles, along with subsequent mono immunotherapy as maintenance therapy for three additional cycles. Following this, the left pleural tumor shrank significantly, and the patient achieved partial remission. However, due to the patient's irregular treatment adherence, the patient returned for systemic immunotherapy therapy for four cycles in November 2021, and a slight reduction of the pleural tumor was achieved. Once again, the patient discontinued treatment until he experienced left-sided chest pain and partial tumor enlargement in February 2023. Another three cycles of immunotherapy were administered, but the pleural tumor continued to grow. In June 2023, the patient succumbed to respiratory failure caused by a pulmonary infection. Overall, the patient's survival time was 76 months.
    Conclusions: Cytoreductive video-assisted thoracic surgery plus hyperthermic intrathoracic chemotherapy followed by systemic chemo-immunotherapy can effectively control pleural effusion, prolong patient survival, and improve the quality of life in patients with MPM.
    Keywords:  Malignant pleural mesothelioma (MPM); case report; chemo-immunotherapy; cytoreductive surgery; video-assisted thoracic surgery (VATS)
    DOI:  https://doi.org/10.21037/jtd-24-1700
  5. Palliat Med. 2024 Dec 17. 2692163241302454
       BACKGROUND: Pleural mesothelioma is a rare and incurable cancer, with complex physical and psychological symptoms. Despite recent advances in treatment, prognosis remains poor (average 8-15 months) with a lack of research on palliative and end-of-life care.
    AIM: To examine markers suggestive of quality palliative and end-of-life care, including receipt of specialist palliative care, advance care planning, fewer unplanned hospital admissions at end-of-life. To compare variables with socio-economic position to identify if inequalities exist.
    DESIGN: A cohort study, retrospectively reviewing the medical notes from diagnosis to death for all patients diagnosed with pleural mesothelioma between 01/01/2016 and 31/12/2021.
    SETTING/PARTICIPANTS: Over 5 years, n = 181 patients were diagnosed with pleural mesothelioma across Teesside (north-east England), n = 30 were alive at study commencement and excluded. For the 151-patient cohort, demographics were as follows: 92% male, 79% aged 70-89 years and 26% in the lowest socio-economic quintile (based on area-level deprivation).
    RESULTS: Median survival was 246 days. Within the final 90 days of life, 69% of patients had at least 1 unplanned hospital admission, with 20% having 3+ (range 0-7). Those with the highest socio-economic position had less admissions on average. Specialist palliative care was received by patients, at home 34%, in hospital 26%, in hospice 11%. Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decisions, were in the final 24 h of life for 18% of patients (median 7 days). Disease specific findings included police attendance for expected deaths and lack of signposting.
    CONCLUSION: Patients with pleural mesothelioma have unplanned admissions to hospital towards the end of life, with possible inequalities; they receive late advance care planning and face challenges unique to their disease. It is important that patients receive high quality palliative end-of-life care through accessing specialist palliative care or have guidance/signposting to other potential sources of support.
    Keywords:  Mesothelioma; advance care planning; coroner; delivery of healthcare; inequalities; palliative care; pleural neoplasms; socio-economic position
    DOI:  https://doi.org/10.1177/02692163241302454
  6. Epidemiol Prev. 2024 Nov-Dec;48(6):48(6): 429-437
       OBJECTIVES: to provide an overview of the geographical distribution of mesothelioma and asbestosis deaths in the Campania Region (Southern Italy) occurred from 2005 to 2018 and to identify areas at higher risk.
    DESIGN: for each municipality, Standardized Mortality Ratios (SMRs) for mesothelioma and asbestosis have been estimated from the mortality data provided by the Italian National Institute of Statistics (Istat). Deaths for which mesothelioma and asbestosis were identified as the underlying causes, according to the classification system ICD-10 codes (C45 and J61, respectively), were included. Expected cases were estimated applying age- and gender-specific mortality rates in Campania on resident populations of each municipality. Furthermore, the association between the municipal SMR and the local socioeconomic deprivation index based on the 2011 General Census of Population and Housing was also analysed.
    SETTING AND PARTICIPANTS: Campania Region.
    MAIN OUTCOMES MEASURES: the study outcomes were standardized mortality ratios for mesothelioma and asbestosis and the identification of territorial subareas.
    RESULTS: a total of 998 deaths attributed to mesothelioma and 62 to asbestosis were identified. No cases of death due to mesothelioma or asbestosis were reported in the province of Benevento. A significant increase in mortality due to mesothelioma was observed across 34 municipalities. These findings show that several municipalities within the province of Naples display a high increase in mortality due to mesothelioma and asbestosis, with 506 deaths in total and 246 cases recorded in the municipality of Naples against 178,37 expected (SMR 1,38; 90%CI 1.24-1.53). In 15 municipalities, a notable increase in mortality for asbestosis was recorded; in Naples, 28 cases occurred (SMR 2,51; 90%CI 1.84-3.42). The overlap between mortality maps for mesothelioma and asbestosis confirms the existence of areas subjected to definite and prolonged asbestos exposure. Additionally, a correlation with the deprivation index was noted: the pooled SMR by quintiles increases with higher quintiles of the deprivation index, for both mesothelioma and asbestosis.
    CONCLUSIONS: results highlight the crucial need for epidemiological surveillance of asbestos-related diseases in Campania. Actively searching out for new cases of mesothelioma in the entire region is a crucial task in primary prevention of occupational, environmental, and domestic exposures to asbestos.
    Keywords:  Asbestos; Asbestosis; Campania Region; Epidemiological surveillance; Mesothelioma
    DOI:  https://doi.org/10.19191/EP24.6.A754.134
  7. Med Lav. 2024 Dec 19. 115(6): e2024042
      The discovery of the detrimental effects of asbestos on human health came long after its widespread use, with the first scientific evidence of asbestos-related diseases emerging in the late 19th and early 20th centuries. Despite efforts to ban its use, asbestos continues to be mined and used in Central Asia (as well as in Russia, China, and other countries). To gain a deeper understanding of the situation in Central Asia, we have conducted a systematic review of scientific literature on the use of asbestos, exposure assessment, and health consequences of asbestos exposure in this geographic area. This review encompasses studies about exposure assessments, epidemiological data, and biochemical or clinical surveys conducted in Kazakhstan, Uzbekistan, Tajikistan, Turkmenistan, and Kyrgyzstan. A total of 18 articles met the inclusion criteria, and their content is summarised in this review, which represents the first attempt to systematically examine research on asbestos and its impact on the health of workers and the general population in Central Asia countries, including literature published in Russian and English. The findings here highlighted the substantial limitations of the currently available knowledge about the impact of asbestos on health in this geographical area.
    DOI:  https://doi.org/10.23749/mdl.v115i6.15453