Cytotoxic T Cells in PD-L1–Positive Malignant Pleural Mesotheliomas Are Counterbalanced by Distinct Immunosuppressive Factors

作者: Mark M. Awad , Robert E. Jones , Hongye Liu , Patrick H. Lizotte , Elena V. Ivanova

DOI: 10.1158/2326-6066.CIR-16-0171

关键词: CD8Interleukin 21CD38Cytotoxic T cellFOXP3Immune systemBiphasic MesotheliomaImmune checkpointPathologyBiology

摘要: PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive PD-L1-negative malignant pleural mesothelioma samples. developed method for phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions applied this technique analyze 43 resected specimens. Compared tumors, had significantly more infiltrating CD45+ cells, higher proportion CD3+ T percentage cells displaying activated HLA-DR+/CD38+ phenotype. also proliferating CD8+ fraction FOXP3+/CD4+ Tregs, increased TIM-3 CD4+ cells. Double-positive PD-1+/TIM-3+ were commonly found tumors. epithelioid sarcomatoid biphasic samples likely be positive showed infiltration Immunologic phenotypes differ based status histologic subtype. Successful incorporation comprehensive profiling by prospective clinical trials could refine our ability which patients specific checkpoint blockade strategies. Cancer Immunol Res; 4(12); 1038-48. ©2016 AACR.

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