دورية أكاديمية
Dynamics of Tumor and Immune Responses during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer.
| العنوان: | Dynamics of Tumor and Immune Responses during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer. |
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| المؤلفون: | Anagnostou V; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. vanagno1@jhmi.edu velculescu@jhmi.edu.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland., Forde PM; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland., White JR; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Niknafs N; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Hruban C; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Naidoo J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland., Marrone K; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland., Sivakumar IKA; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland.; Applied Physics Laboratory, Laurel, Maryland., Bruhm DC; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Rosner S; Department of Internal Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Phallen J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Leal A; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Adleff V; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Smith KN; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland., Cottrell TR; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Rhymee L; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Palsgrove DN; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Hann CL; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Levy B; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Feliciano J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Georgiades C; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Verde F; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Illei P; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Li QK; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Gabrielson E; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Brock MV; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Isbell JM; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, New York., Sauter JL; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Taube J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Scharpf RB; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Karchin R; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland., Pardoll DM; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland., Chaft JE; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York., Hellmann MD; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York., Brahmer JR; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland., Velculescu VE; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. vanagno1@jhmi.edu velculescu@jhmi.edu.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland. |
| المصدر: | Cancer research [Cancer Res] 2019 Mar 15; Vol. 79 (6), pp. 1214-1225. Date of Electronic Publication: 2018 Dec 12. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung/*immunology , Circulating Tumor DNA/*analysis , DNA, Neoplasm/*analysis , Lung Neoplasms/*immunology , Neoplasm, Residual/*immunology , Nivolumab/*therapeutic use, Antineoplastic Agents, Immunological/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Circulating Tumor DNA/genetics ; Cohort Studies ; DNA, Neoplasm/genetics ; Follow-Up Studies ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Neoplasm, Residual/drug therapy ; Neoplasm, Residual/genetics ; Neoplasm, Residual/pathology ; Prognosis ; Survival Rate |
| مستخلص: | Despite the initial successes of immunotherapy, there is an urgent clinical need for molecular assays that identify patients more likely to respond. Here, we report that ultrasensitive measures of circulating tumor DNA (ctDNA) and T-cell expansion can be used to assess responses to immune checkpoint blockade in metastatic lung cancer patients ( N = 24). Patients with clinical response to therapy had a complete reduction in ctDNA levels after initiation of therapy, whereas nonresponders had no significant changes or an increase in ctDNA levels. Patients with initial response followed by acquired resistance to therapy had an initial drop followed by recrudescence in ctDNA levels. Patients without a molecular response had shorter progression-free and overall survival compared with molecular responders [5.2 vs. 14.5 and 8.4 vs. 18.7 months; HR 5.36; 95% confidence interval (CI), 1.57-18.35; P = 0.007 and HR 6.91; 95% CI, 1.37-34.97; P = 0.02, respectively], which was detected on average 8.7 weeks earlier and was more predictive of clinical benefit than CT imaging. Expansion of T cells, measured through increases of T-cell receptor productive frequencies, mirrored ctDNA reduction in response to therapy. We validated this approach in an independent cohort of patients with early-stage non-small cell lung cancer ( N = 14), where the therapeutic effect was measured by pathologic assessment of residual tumor after anti-PD1 therapy. Consistent with our initial findings, early ctDNA dynamics predicted pathologic response to immune checkpoint blockade. These analyses provide an approach for rapid determination of therapeutic outcomes for patients treated with immune checkpoint inhibitors and have important implications for the development of personalized immune targeted strategies. Significance: Rapid and sensitive detection of circulating tumor DNA dynamic changes and T-cell expansion can be used to guide immune targeted therapy for patients with lung cancer. See related commentary by Zou and Meyerson, p. 1038 . (©2018 American Association for Cancer Research.) |
| التعليقات: | Comment in: Cancer Res. 2019 Mar 15;79(6):1038-1040. (PMID: 30877100) |
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| معلومات مُعتمدة: | T32 GM007814 United States GM NIGMS NIH HHS; T32 CA193145 United States CA NCI NIH HHS; R01 CA121113 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; T32 GM008752 United States GM NIGMS NIH HHS; UL1 TR001079 United States TR NCATS NIH HHS; P30 CA006973 United States CA NCI NIH HHS; U10 CA180950 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Antineoplastic Agents, Immunological) 0 (Circulating Tumor DNA) 0 (DNA, Neoplasm) 31YO63LBSN (Nivolumab) |
| تواريخ الأحداث: | Date Created: 20181214 Date Completed: 20191218 Latest Revision: 20201107 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6432636 |
| DOI: | 10.1158/0008-5472.CAN-18-1127 |
| PMID: | 30541742 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
|---|---|
| DOI: | 10.1158/0008-5472.CAN-18-1127 |