Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures Journal Article

Authors: Şenbabaoğlu, Y.; Gejman, R. S.; Winer, A. G.; Liu, M.; Van Allen, E. M.; de Velasco, G.; Miao, D.; Ostrovnaya, I.; Drill, E.; Luna, A.; Weinhold, N.; Lee, W.; Manley, B. J.; Khalil, D. N.; Kaffenberger, S. D.; Chen, Y.; Danilova, L.; Voss, M. H.; Coleman, J. A.; Russo, P.; Reuter, V. E.; Chan, T. A.; Cheng, E. H.; Scheinberg, D. A.; Li, M. O.; Choueiri, T. K.; Hsieh, J. J.; Sander, C.; Hakimi, A. A.
Article Title: Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures
Abstract: Background: Tumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types. Results: We compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8+ T/Treg ratio are associated with improved survival, whereas Th2 cells and Tregs are associated with negative outcomes. Investigation of the association of immune infiltration patterns with the subclonal architecture of tumors shows that both APM and T cell levels are negatively associated with subclone number. Conclusions: Our analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC. © 2016 The Author(s).
Keywords: cancer immunotherapy; checkpoint blockade; tumor immune microenvironment; clear cell renal cell carcinoma (ccrcc); computational deconvolution
Journal Title: Genome Biology
Volume: 17
ISSN: 1465-6906
Publisher: Biomed Central Ltd  
Date Published: 2016-11-17
Start Page: 231
Language: English
DOI: 10.1186/s13059-016-1092-z
PROVIDER: scopus
PMCID: PMC5114739
PUBMED: 27855702
Notes: Erratum issued; see DOI: 10.1186/s13059-017-1180-8 -- Export Date: 3 January 2017 -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    181 Coleman
  2. Timothy Chan
    206 Chan
  3. Paul Russo
    443 Russo
  4. Martin Henner Voss
    123 Voss
  5. Yingbei Chen
    220 Chen
  6. Mingyu Liu
    3 Liu
  7. James J Hsieh
    114 Hsieh
  8. Emily H Cheng
    55 Cheng
  9. Chris Sander
    196 Sander
  10. Ming Li
    65 Li
  11. Victor Reuter
    890 Reuter
  12. Andrew Gordon Winer
    18 Winer
  13. Danny Nejad Khalil
    8 Khalil
  14. William Lee
    38 Lee
  15. Abraham Ari Hakimi
    127 Hakimi
  16. Esther Naomi Drill
    24 Drill
  17. Augustin Luna
    9 Luna
  18. Ron Shlomo Gejman
    8 Gejman
  19. Brandon John Manley
    21 Manley