{
  "abstract": "A 52-year-old man presented with sarcomatoid diffuse pleural mesothelioma that had relapsed at an isolated site after a complete response to dual-immune checkpoint inhibition (ICI). 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+ 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+ and CD4+ T cells are seen in the peripheral blood at relapse. TAMs were enriched in antigen-presentation (CD80, CD86, CXCL10), extracellular matrix–degradation (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—rather than by immune evasion or stromal exclusion—served as a mechanism of acquired resistance to dual-ICI therapy.",
  "authors": [
    {
      "affiliations": [
        "Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Hely Ollila"
    },
    {
      "affiliations": [
        "Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Prateek Kulkarni"
    },
    {
      "affiliations": [
        "Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Hyojin Kim"
    },
    {
      "affiliations": [
        "Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Pratiti Ankola"
    },
    {
      "affiliations": [
        "Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Navin K Chintala"
    },
    {
      "affiliations": [
        "Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Carlos Thomas"
    },
    {
      "affiliations": [
        "Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Jennifer L Sauter"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Michael Offin"
    },
    {
      "affiliations": [
        "Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Prasad S Adusumilli"
    }
  ],
  "title": "Regional immunosuppression and associated systemic markers in focally relapsed sarcomatoid mesothelioma: case report",
  "uid": "0941082a-2374-534b-ae0d-1abf2b3f4877"
}