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Targeted sequencing exhibited amplification of chromosome 9p24, encompassing JAK2, PD-L1, PD-L2, and PTPRD in the relapsed (post-ICI) tumor, compared with baseline (pre-ICI). On multiplex immunofluorescence, tumor-associated macrophages (TAMs) and CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T lymphocytes (CTLs) made up most of the cells in baseline and relapsed tumor (59% and 47%, respectively). Baseline tumor cells expressed genes linked to extracellular matrix remodeling and epithelial-mesenchymal transition, intermixed with M2-like TAMs and tissue-resident, effector-like CTLs. Relapsed tumor cells shifted to a growth factor-driven phenotype (NT5E, NOD1, GATA2, FN1, PDCD1LG2) that is known to cause functional impairment of CTLs, which then transitioned to an exhausted state (FCRL3, CST7, GPR171, TRAT1, LAG3); exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells are seen in the peripheral blood at relapse. TAMs were enriched in antigen-presentation (CD80, CD86, CXCL10), extracellular matrix\u2013degradation (MMP9, CTSL), and CTL-suppression (ARG1, PLA2G7) pathways. Our analyses revealed that regional immunosuppression mediated by adaptive reprogramming of tumor-cell and immune-cell (TAMs, CTLs)-intrinsic changes\u2014rather than by immune evasion or stromal exclusion\u2014served as a mechanism of acquired resistance to dual-ICI therapy.\n                  <\/jats:p>","DOI":"10.1136\/jitc-2025-014516","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T19:05:21Z","timestamp":1776279921000},"page":"e014516","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Regional immunosuppression and associated systemic markers in focally relapsed sarcomatoid mesothelioma: case report"],"prefix":"10.1136","volume":"14","author":[{"given":"Hely","family":"Ollila","sequence":"first","affiliation":[{"name":"Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, 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