Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

Cancer Cell. 2021 Jun 14;39(6):845-865.e7. doi: 10.1016/j.ccell.2021.04.014. Epub 2021 May 20.


The clinical use of molecular targeted therapy is rapidly evolving but has primarily focused on genomic alterations. Transcriptomic analysis offers an opportunity to dissect the complexity of tumors, including the tumor microenvironment (TME), a crucial mediator of cancer progression and therapeutic outcome. TME classification by transcriptomic analysis of >10,000 cancer patients identifies four distinct TME subtypes conserved across 20 different cancers. The TME subtypes correlate with patient response to immunotherapy in multiple cancers, with patients possessing immune-favorable TME subtypes benefiting the most from immunotherapy. Thus, the TME subtypes act as a generalized immunotherapy biomarker across many cancer types due to the inclusion of malignant and microenvironment components. A visual tool integrating transcriptomic and genomic data provides a global tumor portrait, describing the tumor framework, mutational load, immune composition, anti-tumor immunity, and immunosuppressive escape mechanisms. Integrative analyses plus visualization may aid in biomarker discovery and the personalization of therapeutic regimens.

Keywords: biomarker discovery; cancer; genomics; integrated analysis; transcriptomics; tumor microenvironment classification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / pathology
  • Data Visualization
  • Databases, Factual
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunotherapy / methods*
  • Melanoma / genetics
  • Melanoma / immunology
  • Melanoma / pathology
  • Neoplasms / etiology*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Precision Medicine
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Treatment Outcome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*


  • Immune Checkpoint Inhibitors