{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:35:19Z","timestamp":1792852519904,"version":"4.5.0"},"reference-count":123,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"unspecified","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015182","name":"Hope Against Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015182","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2021,8,6]]},"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p>Malignant pleural mesothelioma (MPM) is an incurable cancer with a dismal prognosis and few effective treatment options. Nonetheless, recent positive phase III trial results for immune checkpoint blockade (ICB) in MPM herald a new dawn in the fight to advance effective treatments for this cancer. Tumor mutation burden (TMB) has been widely reported to predict ICB in other cancers, but MPM is considered a low-TMB tumor. Similarly, tumor programmed death-ligand 1 (PD-L1) expression has not been proven predictive in phase III clinical trials in MPM. Consequently, the precise mechanisms that determine response to immunotherapy in this cancer remain unknown. The present review therefore aimed to synthesize our current understanding of the tumor immune microenvironment in MPM and reflects on how specific cellular features might impact immunotherapy responses or lead to resistance. This approach will inform stratified approaches to therapy and advance immunotherapy combinations in MPM to improve clinical outcomes further.<\/jats:p>","DOI":"10.1136\/jitc-2021-003032","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T11:32:37Z","timestamp":1631532757000},"page":"e003032","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6451-9598","authenticated-orcid":false,"given":"James","family":"Harber","sequence":"first","affiliation":[{"name":"Cancer Research Centre, University of Leicester College of Life Sciences, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamihiro","family":"Kamata","sequence":"additional","affiliation":[{"name":"Cancer Research Centre, University of Leicester College of Life Sciences, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catrin","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Cancer Research Centre, University of Leicester College of Life Sciences, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Fennell","sequence":"additional","affiliation":[{"name":"Cancer Research Centre, University of Leicester College of Life Sciences, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"2025100312293395000_9.9.e003032.1","first-page":"260","article-title":"Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province","volume":"17","author":"Wagner","year":"1960","journal-title":"Br J Ind Med"},{"key":"2025100312293395000_9.9.e003032.2","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.128474","article-title":"Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1-dependent mechanism","volume":"4","author":"Hamaidia","year":"2019","journal-title":"JCI Insight"},{"key":"2025100312293395000_9.9.e003032.3","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3481"},{"key":"2025100312293395000_9.9.e003032.4","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtho.2020.08.004","article-title":"ID:2908 first-line nivolumab + ipilimumab vs chemotherapy in unresectable malignant pleural mesothelioma: CheckMate 743","volume":"15","author":"Baas","year":"2020","journal-title":"J Thor Oncol"},{"key":"2025100312293395000_9.9.e003032.5","unstructured":"Fennell DA . 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