Journal
CLINICAL CANCER RESEARCH
Volume 26, Issue 13, Pages 3296-3306Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-19-3294
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Funding
- Division of Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research
- NIH [CA032685, CA166105, CA197078, GM067386]
- Clinical and Translational Science Award [1TL1RR025013-01]
- Cancer Center Support Grant [P30 CA014520]
- Midwest Athletes for Childhood Cancer Fund
- Ann's Hope Foundation
- Tim Eagle Memorial
- Jay Van Sloan Memorial from the Steve Leuthold Family
- Stand Up To Cancer - St. Baldrick's Pediatric Dream Team Translational Research Grant [SU2C-AACR-DT1113]
- NATIONAL CANCER INSTITUTE [ZIABC011002] Funding Source: NIH RePORTER
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Purpose: We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, to identify predictive immune and/or tumor biomarkers in patients with melanoma at high risk for recurrence. Experimental Design: Patients were randomly assigned to receive the first of three monthly courses of hu14.18-IL2 immunotherapy either before (Group A) or after (Group B) complete surgical resection of all known diseases. Tumors were evaluated by histology and whole transcriptome sequencing. Results: Tumor-infiltrating lymphocyte (TIL) levels directly associated with relapse-free survival (RFS) and overall survival (OS) in resected tumors from Group A, where early responses to the immunotherapy agent could be assessed. TIL levels directly associated with a previously reported immune signature, which associated with RFS and OS, particularly in Group A tumors. In Group A tumors, there were decreased cell-cycling gene RNA transcripts, but increased RNA transcripts for repair and growth genes. We found that outcome (RFS and OS) was directly associated with several immune signatures and immune-related RNA transcripts and inversely associated with several tumor growth-associated transcripts, particularly in Group A tumors. Most of these associations were not seen in Group B tumors. Conclusions: We interpret these data to signify that both immunologic and tumoral cell processes, as measured by RNA-sequencing analyses detected shortly after initiation of hu14.18-IL2 therapy, are associated with long-term survival and could potentially be used as prognostic biomarkers in tumor resection specimens obtained after initiating neoadjuvant immunotherapy.
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