T‐cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death‐ligand 1 expression in patients with soft tissue sarcomas

作者：Seth M. Pollack, Qianchuan He, Jennifer Holmes Yearley, Ryan Emerson, Marissa Vignali, Yuzheng Zhang, Mary Weber Redman, Kelsey K. Baker, Sara J. Cooper, Bailey Donahue, Elizabeth T. Loggers, Lee D. Cranmer, Matthew B. Spraker, Yongwoo David Seo, Venu Gopal Pillarisetty, Robert W. Ricciotti, Benjamin L. Hoch, Terrill K. McClanahan, Erin Elizabeth Murphy, Wendy M. Blumenschein, Steven Matthew Townson, Sharon Benzeno, Stanley R. Riddell, Robin L. Jones · 发表于：Cancer · 年份：2017 · DOI：10.1002/cncr.30726 · 被引用次数：277 · 研究领域：Sarcoma Diagnosis and Treatment、Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers

BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vβ gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated. RESULTS: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01). CONCLUSIONS: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarc...