{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:14:00Z","timestamp":1791335640381,"version":"4.3.1"},"reference-count":71,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Multiplex Immunofluorescence and Image Analysis Laboratory","award":["2018\/20403-6"],"award-info":[{"award-number":["2018\/20403-6"]}]},{"name":"Multiplex Immunofluorescence and Image Analysis Laboratory","award":["2019\/12151-0"],"award-info":[{"award-number":["2019\/12151-0"]}]},{"name":"Multiplex Immunofluorescence and Image Analysis Laboratory","award":["2023\/02755-0"],"award-info":[{"award-number":["2023\/02755-0"]}]},{"name":"Multiplex Immunofluorescence and Image Analysis Laboratory","award":["303735\/2021-0"],"award-info":[{"award-number":["303735\/2021-0"]}]},{"name":"Sao Paulo Research Foundation","award":["2018\/20403-6"],"award-info":[{"award-number":["2018\/20403-6"]}]},{"name":"Sao Paulo Research Foundation","award":["2019\/12151-0"],"award-info":[{"award-number":["2019\/12151-0"]}]},{"name":"Sao Paulo Research Foundation","award":["2023\/02755-0"],"award-info":[{"award-number":["2023\/02755-0"]}]},{"name":"Sao Paulo Research Foundation","award":["303735\/2021-0"],"award-info":[{"award-number":["303735\/2021-0"]}]},{"name":"National Council for Scientific and Technological Development","award":["2018\/20403-6"],"award-info":[{"award-number":["2018\/20403-6"]}]},{"name":"National Council for Scientific and Technological Development","award":["2019\/12151-0"],"award-info":[{"award-number":["2019\/12151-0"]}]},{"name":"National Council for Scientific and Technological Development","award":["2023\/02755-0"],"award-info":[{"award-number":["2023\/02755-0"]}]},{"name":"National Council for Scientific and Technological Development","award":["303735\/2021-0"],"award-info":[{"award-number":["303735\/2021-0"]}]},{"name":"University of Sao Paulo Medical School","award":["2018\/20403-6"],"award-info":[{"award-number":["2018\/20403-6"]}]},{"name":"University of Sao Paulo Medical School","award":["2019\/12151-0"],"award-info":[{"award-number":["2019\/12151-0"]}]},{"name":"University of Sao Paulo Medical School","award":["2023\/02755-0"],"award-info":[{"award-number":["2023\/02755-0"]}]},{"name":"University of Sao Paulo Medical School","award":["303735\/2021-0"],"award-info":[{"award-number":["303735\/2021-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Several tumor-associated macrophages (TAMs) have shown promise as prognosticators in cancer. Our aim was to validate the importance of TAMs in malignant pleural mesothelioma (MPM) using a two-stage design. Methods: We explored The Cancer Genome Atlas (TCGA-MESO) to select immune-relevant macrophage genes in MPM, including M1\/M2 markers, as a discovery cohort. This computational cohort was used to create a multiplex immunofluorescence panel. Moreover, a cohort of 68 samples of MPM in paraffin blocks was used to validate the macrophage phenotypes and the co-localization and spatial distribution of these immune cells within the TME and the stromal or tumor compartments. Results: The discovery cohort revealed six immune-relevant macrophage genes (CD68, CD86, CD163, CD206, ARG1, CD274), and complementary genes were differentially expressed by M1 and M2 phenotypes with distinct roles in the tumor microenvironment and were associated with the prognosis. In addition, immune-suppressed MPMs with increased enrichment of CD68, CD86, and CD163 genes and high densities of M2 macrophages expressing CD163 and CD206 proteins were associated with worse overall survival (OS). Interestingly, below-median distances from malignant cells to specific M2a and M2c macrophages were associated with worse OS, suggesting an M2 macrophage-driven suppressive component in these tumors. Conclusions: The interactions between TAMs in situ and, particularly, CD206+ macrophages are highly relevant to patient outcomes. High-resolution technology is important for identifying the roles of macrophage populations in tissue specimens and identifying potential therapeutic candidates in MPM.<\/jats:p>","DOI":"10.3390\/cancers15215116","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:29:01Z","timestamp":1698128941000},"page":"5116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Immunological Landscape of M1 and M2 Macrophages and Their Spatial Distribution in Patients with Malignant Pleural Mesothelioma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-6123","authenticated-orcid":false,"given":"Caddie","family":"Laberiano-Fernandez","sequence":"first","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5364-7305","authenticated-orcid":false,"given":"Camila Machado","family":"Baldavira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3984-4959","authenticated-orcid":false,"given":"Juliana","family":"Machado-Rugolo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auriole","family":"Tamegnon","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renganayaki Krishna","family":"Pandurengan","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre Muxfeldt","family":"Ab\u2019Saber","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"},{"name":"Division of Pneumology, Instituto do Cora\u00e7\u00e3o (Incor), Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-8414","authenticated-orcid":false,"given":"Marcelo Luiz","family":"Balancin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"},{"name":"Division of Pneumology, Instituto do Cora\u00e7\u00e3o (Incor), Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-2100","authenticated-orcid":false,"given":"Teresa Yae","family":"Takagaki","sequence":"additional","affiliation":[{"name":"Division of Pneumology, Instituto do Cora\u00e7\u00e3o (Incor), Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0728-4937","authenticated-orcid":false,"given":"Maria Aparecida","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Radiology and Oncology, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"},{"name":"Laboratory of Molecular Genetics, Center for Translational Research in Oncology, Cancer Institute of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-5853","authenticated-orcid":false,"given":"Vera Luiza","family":"Capelozzi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"},{"name":"Division of Pneumology, Instituto do Cora\u00e7\u00e3o (Incor), Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-1636","authenticated-orcid":false,"given":"Edwin Roger","family":"Parra","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, 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