A pan-cancer approach to predict responsiveness to immune checkpoint inhibitors by machine learning

Maurizio Polano, Marco Chierici, Michele Dal Bo, Davide Gentilini, Federica Di Cintio, Lorena Baboci, David L. Gibbs, Cesare Furlanello, Giuseppe Toffoli

Research output: Contribution to journalArticle

Abstract

Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by a specific cancer. Thus, it becomes crucial to identify factors that predict the response to immunotherapeutic approaches. A comprehensive investigation of the mutational and immunological aspects of the tumor can be useful to obtain a robust prediction. By performing a pan-cancer analysis on gene expression data from the Cancer Genome Atlas (TCGA, 8055 cases and 29 cancer types), we set up and validated a machine learning approach to predict the potential for positive response to ICI. Support vector machines (SVM) and extreme gradient boosting (XGboost) models were developed with a 10×5-fold cross-validation schema on 80% of TCGA cases to predict ICI responsiveness defined by a score combining tumor mutational burden and TGF-β signaling. On the remaining 20% validation subset, our SVM model scored 0.88 accuracy and 0.27 Matthews Correlation Coefficient. The proposed machine learning approach could be useful to predict the putative response to ICI treatment by expression data of primary tumors.

Original languageEnglish
Article number1562
JournalCancers
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 2019

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Keywords

  • Immune checkpoint inhibitor
  • Immunology-pancancer
  • Machine learning

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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