Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

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. [Display omitted] •Development of a holistic transcriptomic-based TME classification platform•Detection of four immune/fibrotic TME subtypes conserved in a broad array of cancers•The four TME subtypes are predictive of response to immunotherapy in multiple cancers•Integration of genomics and transcriptomics into a visual tool with a planetary view Bagaev et al. identify four tumor microenvironment (TME) subtypes that are conserved across diverse cancers and correlate with immunotherapy response in melanoma, bladder, and gastric cancers. A visual tool revealing the TME subtypes integrated with targetable genomic alterations provides a planetary view of each tumor that can aid in oncology clinical decision making.