دورية أكاديمية
T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas.
| العنوان: | T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. |
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| المؤلفون: | Pollack, SM, He, Q, Yearley, JH, Emerson, R, Vignali, M, Zhang, Y, Redman, MW, Baker, KK, Cooper, S, Donahue, B, Loggers, ET, Cranmer, LD, Spraker, MB, Seo, YD, Pillarisetty, VG, Ricciotti, RW, Hoch, BL, McClanahan, TK, Murphy, E, Blumenschein, WM, Townson, SM, Benzeno, S, Riddell, SR, Jones, RL |
| المساهمون: | Jones, Robin, Marsden |
| سنة النشر: | 2018 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | T-Lymphocytes, Clone Cells, Humans, Sarcoma, Soft Tissue Neoplasms, Neoplasm Invasiveness, Biopsy, Needle, Neoplasm Staging, Prognosis, Disease-Free Survival, Combined Modality Therapy, Immunohistochemistry, Analysis of Variance, Cluster Analysis, Survival Analysis, Retrospective Studies, Cohort Studies, Gene Expression Regulation, Neoplastic, Databases, Factual, Adult, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Programmed Cell Death 1 Receptor |
| الوصف: | 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 sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; 3304; image/png |
| اللغة: | English |
| تدمد: | 0008-543X 1097-0142 |
| العلاقة: | Cancer, 2017, 123 (17), pp. 3291 - 3304; https://repository.icr.ac.uk/handle/internal/1074Test |
| DOI: | 10.1002/cncr.30726 |
| الإتاحة: | https://doi.org/10.1002/cncr.30726Test https://repository.icr.ac.uk/handle/internal/1074Test |
| حقوق: | https://creativecommons.org/licenses/by-nc/4.0Test |
| رقم الانضمام: | edsbas.FC680BB6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 0008543X 10970142 |
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| DOI: | 10.1002/cncr.30726 |