{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:52:28Z","timestamp":1787017948553,"version":"build-2736575974"},"reference-count":37,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"abstract":"<jats:p>Introduction: Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated. Methods: In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers: CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1, and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed. Results: Among the immune cell markers, CD3 (p &amp;lt; 0.0001), CD4 (p = 0.0016), CD8 (p = 0.00094), CD163+ (p = 0.042), and FOXP3+ (p = 0.025) were significantly associated with an unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (p = 0.050), CD27 (p = 0.014), and TIM-3 (p = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (p = 0.016): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (p = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04), and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients. Conclusion: Our findings indicate immune checkpoint and\/or immune cell-targeting therapies against CD70-CD27 and\/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.<\/jats:p>","DOI":"10.1159\/000538520","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T17:00:49Z","timestamp":1717434049000},"page":"313-325","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Pleural Mesothelioma by Hierarchical Clustering Analyses Using Immune Cells within Tumor 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