American Association for Cancer Research
10780432ccr193294-sup-230299_2_supp_6121971_q6c469.pptx (51.8 kB)

Supplemental Figure SF-15 from Outcome-Related Signatures Identified by Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated after Starting Hu14.18-IL2

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posted on 2023-03-31, 22:02 authored by Richard K. Yang, Igor B. Kuznetsov, Erik A. Ranheim, Jun S. Wei, Sivasish Sindiri, Berkley E. Gryder, Vineela Gangalapudi, Young K. Song, Viharkumar Patel, Jacquelyn A. Hank, Cindy Zuleger, Amy K. Erbe, Zachary S. Morris, Renae Quale, KyungMann Kim, Mark R. Albertini, Javed Khan, Paul M. Sondel

Expanded Pathway-Level Enrichment Analysis of Gene Sets Whose Expression Correlates with Overall Survival in Group A Patients



Clinical and Translational Science





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. 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. 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. 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.