التفاصيل البيبلوغرافية
| العنوان: |
Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy |
| المؤلفون: |
Mitesh J Borad, Giannoula Karagouga, Jun Yin, Stephen Murphy, Paul Baas, James Smadbeck, John Cheville, Alexa McCune, Aaron Mansfield, George Vasmatzis, Aakash P Desai, Farhad Kosari, Maria Disselhorst, Alireza Agahi, Tobias Peikert, Julia Udell, Sarah H Johnson, Janet Schaefer-Klein |
| المصدر: |
Journal for ImmunoTherapy of Cancer, Vol 11, Iss 6 (2023) |
| بيانات النشر: |
BMJ Publishing Group, 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: |
Background Immune checkpoint inhibitors (ICIs) are now a first-line treatment option for patients with pleural mesothelioma with the recent approval of ipilimumab and nivolumab. Mesothelioma has a low tumor mutation burden and no robust predictors of survival with ICI. Since ICIs enable adaptive antitumor immune responses, we investigated T-cell receptor (TCR) associations with survival in participants from two clinical trials treated with ICI.Methods We included patients with pleural mesothelioma who were treated with nivolumab (NivoMes, NCT02497508) or nivolumab and ipilimumab (INITIATE, NCT03048474) after first-line therapy. TCR sequencing was performed with the ImmunoSEQ assay in 49 and 39 pretreatment and post-treatment patient peripheral blood mononuclear cell (PBMC) samples. These data were integrated with TCR sequences found in bulk RNAseq data by TRUST4 program in 45 and 35 pretreatment and post-treatment tumor biopsy samples and TCR sequences from over 600 healthy controls. The TCR sequences were clustered into groups of shared antigen specificity using GIANA. Associations of TCR clusters with overall survival were determined by cox proportional hazard analysis.Results We identified 4.2 million and 12 thousand complementarity-determining region 3 (CDR3) sequences from PBMCs and tumors, respectively, in patients treated with ICI. These CDR3 sequences were integrated with 2.1 million publically available CDR3 sequences from healthy controls and clustered. ICI-enhanced T-cell infiltration and expanded T cell diversity in tumors. Cases with TCR clones in the top tertile in the pretreatment tissue or in circulation had significantly better survival than the bottom two tertiles (p |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2051-1426 |
| Relation: |
https://jitc.bmj.com/content/11/6/e006035.full; https://doaj.org/toc/2051-1426 |
| DOI: |
10.1136/jitc-2022-006035 |
| URL الوصول: |
https://doaj.org/article/a6826c67289e41c885adfe1bf7000f0b |
| رقم الانضمام: |
edsdoj.6826c67289e41c885adfe1bf7000f0b |
| قاعدة البيانات: |
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