@article{67366bbc619947c8963c40eba2c49c52,
title = "Conserved pan-cancer microenvironment subtypes predict response to immunotherapy",
abstract = "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",
author = "Alexander Bagaev and Nikita Kotlov and Krystle Nomie and Viktor Svekolkin and Azamat Gafurov and Olga Isaeva and Nikita Osokin and Ivan Kozlov and Felix Frenkel and Olga Gancharova and Nava Almog and Maria Tsiper and Ravshan Ataullakhanov and Nathan Fowler",
note = "Funding Information: We thank Yuriy Frolov for his contribution to the visual tool. We thank Linghua Wang (University of Texas MD Anderson Cancer Center) and Leandro Cerchietti (Weill Cornell Medicine) for their insightful comments on this manuscript. N.F. and R.A. conceived and jointly supervised the study. N.F. R.A. A.B. and N.K. conceived of the experiments. A.B. N.K. and O.I. created and validated the gene expression signatures. A.B. N.K. V.S. A.G. and F.F. conducted the data analyses and raw sequencing data processing. O.G. performed histological assessment of the tissue slides. N.O. and I.K. created the Web-based MF Portrait visual tool. A.B. N.K. and K.N. contributed to figure and table generation for the manuscript. A.B. N.K. K.N. N.A. M.T. R.A. and N.F. wrote and revised the manuscript and prepared the figures. N.F. is the Chief Medical Officer of BostonGene, Corp. and a professor at the University of Texas MD Anderson Cancer Center. This research was funded by BostonGene, Corp. and all authors were employees thereof at the time the study was performed. The authors declare no other competing financial interests. A.B. F.F. N.K. and R.A. are inventors on patents related to the TME classification platform and the visual tool. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = jun,
day = "14",
doi = "10.1016/j.ccell.2021.04.014",
language = "English (US)",
volume = "39",
pages = "845--865.e7",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}