In:
JCO Clinical Cancer Informatics, American Society of Clinical Oncology (ASCO), , No. 6 ( 2022-05)
Abstract:
High tumor mutation burden (TMB) in many cancer types is associated with the production of tumor-specific neoantigens, a favorable outcome and response to immune checkpoint blockade (ICB) therapy. Besides mutation-derived neoantigens, aberrant intron retention also produces tumor neopeptides that could trigger an immune response. The relationship between intron-retention–derived tumor neoantigens (IR-neoAg) and clinical outcomes in pancreatic cancer remains uncertain. Here, we quantify IR-neoAg in pancreatic cancer and evaluate whether IR-neoAg load might serve as a biomarker for selecting patients who may benefit from ICB therapy. METHODS We developed a computational approach to estimate patient-specific IR-neoAg load from transcriptome data available in The Cancer Genome Atlas pancreatic cancer cohort. Associations between IR-neoAg load and patient overall survival were evaluated using Kaplan-Meier estimates and Cox regression. Differential expression of immune checkpoint and HLA-I genes was evaluated in tumors with high IR-neoAg load. RESULTS High IR-neoAg load predicted better overall survival in pancreatic cancer, although no association was found for TMB. IR-neoAg load remained a significant prognostic factor after adjusting for patient age, sex, tumor stage and grade, and TMB. Moreover, pancreatic tumors with both high IR-neoAg load and high HLA-I gene expression had similar gene expression profiles as other tumor types that showed response to anti–programmed cell death protein 1 therapy. CONCLUSION IR-neoAg load is associated with favorable survival in pancreatic cancer. These findings provide strong evidence for considering IR-neoAgs when selecting patients who might benefit from ICB therapy.
Type of Medium:
Online Resource
ISSN:
2473-4276
DOI:
10.1200/CCI.21.00124
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
