@article{cd205449bd0d473fa83c1bf7ea1b46e9,
title = "Outcome-related signatures identified by whole transcriptome sequencing of resectable stage III/IV melanoma evaluated after starting Hu14.18-IL2",
abstract = "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.",
author = "Yang, {Richard K.} and Kuznetsov, {Igor B.} and Ranheim, {Erik A.} and Wei, {Jun S.} and Sivasish Sindiri and Gryder, {Berkley E.} and Vineela Gangalapudi and Song, {Young K.} and Viharkumar Patel and Hank, {Jacquelyn A.} and Cindy Zuleger and Erbe, {Amy K.} and Morris, {Zachary S.} and Renae Quale and Kim, {Kyung Mann} and Albertini, {Mark R.} and Javed Khan and Sondel, {Paul M.}",
note = "Funding Information: The authors thank the UWCCC Melanoma clinical research and laboratory support team for the clinical research involved. They acknowledge contributions by the surgical oncologists participating in this study, including Drs. Sharon Weber, Heather Neuman, Greg Hartig, Tracey Weigel, and David Mahvi, and also contributions by Mary Beth Henry, NP. This study was facilitated by the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (https://hpc.nih.gov/docs/userguide.html), and was enabled by funding from the Division of Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. This work was supported by NIH grants CA032685, CA166105, CA197078 (to P.M. Sondel), GM067386, Clinical and Translational Science Award 1TL1RR025013-01 to the University of Wisconsin Institute for Clinical and Translational Research (to E.A. Ranheim, Z.S. Morris, M.R. Albertini, K. Kim, and P.M. Sondel), Cancer Center Support Grant, P30 CA014520, to the University of Wisconsin Carbone Cancer Center (to E.A. Ranheim, Z.S. Morris, M.R. Albertini, J.A. Hank, K. Kim, and P.M. Sondel), The Midwest Athletes for Childhood Cancer Fund (to J.A. Hank and P.M. Sondel), Ann's Hope Foundation (to M.R. Albertini), the Tim Eagle Memorial (to M.R. Albertini), the Jay Van Sloan Memorial from the Steve Leuthold Family (to M.R. Albertini), and The Stand Up To Cancer - St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). Stand Up To Cancer is a division of the Entertainment Industry Foundation administered by the American Association for Cancer Research. Funding Information: The authors thank the UWCCC Melanoma clinical research and laboratory support team for the clinical research involved. They acknowledge contributions by the surgical oncologists participating in this study, including Drs. Sharon Weber, Heather Neuman, Greg Hartig, Tracey Weigel, and David Mahvi, and also contributions by Mary Beth Henry, NP. This study was facilitated by the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (https://hpc.nih.gov/docs/userguide.html), and was enabled by funding from the Division of Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. This work was supported by NIH grants CA032685, CA166105, CA197078 (to P.M. Sondel), GM067386, Clinical and Translational Science Award 1TL1RR025013-01 to the University of Wisconsin Institute for Clinical and Translational Research (to E.A. Ranheim, Z.S. Morris, M.R. Albertini, K. Kim, and P.M. Sondel), Cancer Center Support Grant, P30 CA014520, to the University of Wisconsin Carbone Cancer Center (to E.A. Ranheim, Z.S. Morris, M.R. Albertini, J.A. Hank, K. Kim, and P.M. Sondel), The Midwest Athletes for Childhood Cancer Fund (to J.A. Hank and P.M. Sondel), Ann's Hope Foundation (to M.R. Albertini), the Tim Eagle Memorial (to M.R. Albertini), the Jay Van Sloan Memorial from the Steve Leuthold Family (to M.R. Albertini), and The Stand Up To Cancer – St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). Stand Up To Cancer is a division of the Entertainment Industry Foundation administered by the American Association for Cancer Research. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = jul,
doi = "10.1158/1078-0432.CCR-19-3294",
language = "English (US)",
volume = "26",
pages = "3296--3306",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "13",
}