Integrative Tumor and Immune Cell Multi-omic Analyses Predict Response to Immune Checkpoint Blockade in Melanoma

Cell Rep Med. 2020 Nov 17;1(8):100139. doi: 10.1016/j.xcrm.2020.100139.


In this study, we incorporate analyses of genome-wide sequence and structural alterations with pre- and on-therapy transcriptomic and T cell repertoire features in immunotherapy-naive melanoma patients treated with immune checkpoint blockade. Although tumor mutation burden is associated with improved treatment response, the mutation frequency in expressed genes is superior in predicting outcome. Increased T cell density in baseline tumors and dynamic changes in regression or expansion of the T cell repertoire during therapy distinguish responders from non-responders. Transcriptome analyses reveal an increased abundance of B cell subsets in tumors from responders and patterns of molecular response related to expressed mutation elimination or retention that reflect clinical outcome. High-dimensional genomic, transcriptomic, and immune repertoire data were integrated into a multi-modal predictor of response. These findings identify genomic and transcriptomic characteristics of tumors and immune cells that predict response to immune checkpoint blockade and highlight the importance of pre-existing T and B cell immunity in therapeutic outcomes.

Trial registration: NCT01621490.

Keywords: T cell repertoire; cancer genomics; immune checkpoint blockade; integrative predictive model; melanoma; multi-omics.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression / immunology
  • Gene Expression Profiling / methods
  • Genomics / methods
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immunotherapy / methods
  • Melanoma / drug therapy*
  • Melanoma / genetics*
  • Melanoma / immunology
  • Mutation / drug effects
  • Mutation / genetics
  • Mutation / immunology
  • Prospective Studies
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology
  • Transcriptome / drug effects
  • Transcriptome / genetics
  • Transcriptome / immunology


  • Immune Checkpoint Inhibitors

Associated data