دورية أكاديمية
Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab.
| العنوان: | Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab. |
|---|---|
| المؤلفون: | Riaz, Nadeem, Havel, Jonathan J, Makarov, Vladimir, Desrichard, Alexis, Urba, Walter, Sims, Jennifer S, Hodi, F Stephen, Martín-Algarra, Salvador, Mandal, Rajarsi, Sharfman, William H, Bhatia, Shailender, Hwu, Wen-Jen, Gajewski, Thomas F, Slingluff, Craig L, Chowell, Diego, Kendall, Sviatoslav M, Chang, Han, Shah, Rachna, Kuo, Fengshen, Morris, Luc G T, Sidhom, John-William, Schneck, Jonathan P, Horak, Christine E, Weinhold, Nils, Chan, Timothy A |
| المصدر: | Articles, Abstracts, and Reports |
| بيانات النشر: | Providence St. Joseph Health Digital Commons |
| سنة النشر: | 2017 |
| المجموعة: | Providence St. Joseph Health Digital Commons |
| مصطلحات موضوعية: | Antibodies, Monoclonal, Antineoplastic Agents, Genome-Wide Association Study, Humans, Immunotherapy, Melanoma, Nivolumab, Programmed Cell Death 1 Receptor, T-Lymphocytes, Transcriptome, Tumor Microenvironment, Oncology |
| الوصف: | The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific transcriptional networks, and upregulation of immune checkpoint genes that were more pronounced in patients with response. Temporal changes in intratumoral TCR repertoire revealed expansion of T cell clones in the setting of neoantigen loss. Comprehensive genomic profiling data in this study provide insight into nivolumab's mechanism of action. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.psjhealth.org/publications/1752Test; https://digitalcommons.psjhealth.org/cgi/viewcontent.cgi?article=2726&context=publicationsTest |
| الإتاحة: | https://digitalcommons.psjhealth.org/publications/1752Test https://digitalcommons.psjhealth.org/cgi/viewcontent.cgi?article=2726&context=publicationsTest |
| رقم الانضمام: | edsbas.5D323EB3 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |