{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:54:41Z","timestamp":1790470481502,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T00:00:00Z","timestamp":1621641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hellenic Thoracic Society","award":["01.2016"],"award-info":[{"award-number":["01.2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Colony-Stimulating Factor 1 (CSF1)\/Colony-Stimulating Factor Receptor 1 (CSF1R) signaling orchestrates tumor-associated macrophage (TAM) recruitment and polarization towards a pro-tumor M2 phenotype, the dominant phenotype of TAMs infiltrating mesothelioma tumors. We hypothesized that CSF1\/CSF1R inhibition would halt mesothelioma growth by targeting immunosuppressive M2 macrophages and unleashing efficient T cell responses. We also hypothesized that CSF1\/CSF1R blockade would enhance the efficacy of a PDL1 inhibitor which directly activates CD8+ cells. We tested a clinically relevant CSF1R inhibitor (BLZ945) in mesothelioma treatment using syngeneic murine models. We evaluated the role of CSF1\/CSF1R axis blockade in tumor-infiltrating immune subsets. We examined the effect of combined anti-CSF1R and anti-PDL1 treatment in mesothelioma progression. CSF1R inhibition impedes mesothelioma progression, abrogates infiltration of TAMs, facilitates an M1 anti-tumor phenotype and activates tumor dendritic and CD8+ T cells. CSF1R inhibition triggers a compensatory PD-1\/PDL1 upregulation in tumor and immune cells. Combined CSF1R inhibitor with an anti-PDL1 agent was more effective in retarding mesothelioma growth compared to each monotherapy. In experimental mesotheliomas, CSF1R inhibition abrogates tumor progression by limiting suppressive myeloid populations and enhancing CD8+ cell activation and acts synergistically with anti-PDL1.<\/jats:p>","DOI":"10.3390\/cancers13112546","type":"journal-article","created":{"date-parts":[[2021,5,23]],"date-time":"2021-05-23T23:58:05Z","timestamp":1621814285000},"page":"2546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["CSF1\/CSF1R Axis Blockade Limits Mesothelioma and Enhances Efficiency of Anti-PDL1 Immunotherapy"],"prefix":"10.3390","volume":"13","author":[{"given":"Sophia Fotiou","family":"Magkouta","sequence":"first","affiliation":[{"name":"Marianthi Simou Laboratory, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 3 Ploutarchou st, 2nd Floor, 10675 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Photene Christou","family":"Vaitsi","sequence":"additional","affiliation":[{"name":"Marianthi Simou Laboratory, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 3 Ploutarchou st, 2nd Floor, 10675 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos Georgiou","family":"Pappas","sequence":"additional","affiliation":[{"name":"Marianthi Simou Laboratory, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 3 Ploutarchou st, 2nd Floor, 10675 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianthi","family":"Iliopoulou","sequence":"additional","affiliation":[{"name":"Marianthi Simou Laboratory, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 3 Ploutarchou st, 2nd Floor, 10675 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrysavgi Nikolaou","family":"Kosti","sequence":"additional","affiliation":[{"name":"Marianthi Simou Laboratory, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 3 Ploutarchou st, 2nd Floor, 10675 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Psarra","sequence":"additional","affiliation":[{"name":"Department of Immunology\u2014Histocompatibility, Evangelismos Hospital, 10675 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis Theodorou","family":"Kalomenidis","sequence":"additional","affiliation":[{"name":"Marianthi Simou Laboratory, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 3 Ploutarchou st, 2nd Floor, 10675 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.canep.2019.03.014","article-title":"Incidence and survival of peritoneal malignant mesothelioma between 1989 and 2015: A population-based study","volume":"60","author":"Bouvier","year":"2019","journal-title":"Cancer Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1093\/ejcts\/ezx427","article-title":"Predictors of Trimodality Therapy Trends in Therapy for Malignant Pleural mesothelioma","volume":"53","author":"Nelson","year":"2018","journal-title":"Eur. 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