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Profiling Tumor Infiltrating Immune Cells with CIBERSORT

Part of the Methods in Molecular Biology book series (MIMB,volume 1711)

Abstract

Tumor infiltrating leukocytes (TILs) are an integral component of the tumor microenvironment and have been found to correlate with prognosis and response to therapy. Methods to enumerate immune subsets such as immunohistochemistry or flow cytometry suffer from limitations in phenotypic markers and can be challenging to practically implement and standardize. An alternative approach is to acquire aggregative high dimensional data from cellular mixtures and to subsequently infer the cellular components computationally. We recently described CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs). Combining support vector regression with prior knowledge of expression profiles from purified leukocyte subsets, CIBERSORT can accurately estimate the immune composition of a tumor biopsy. In this chapter, we provide a primer on the CIBERSORT method and illustrate its use for characterizing TILs in tumor samples profiled by microarray or RNA-Seq.

Key words

  • Cancer immunology
  • Deconvolution
  • Support vector regression (SVR)
  • Tumor infiltrating leukocytes (TILs)
  • Tumor microenvironment
  • Tumor heterogeneity
  • Gene expression
  • Microarray
  • RNA-Seq
  • TCGA

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Acknowledgments

We would like to thank David Steiner, M.D., Ph.D. for his assistance in generating the RNA-Seq derived signature matrix. This work is supported by grants from the Doris Duke Charitable Foundation (A.A.A.), the Damon Runyon Cancer Research Foundation (A.A.A.), the B&J Cardan Oncology Research Fund (A.A.A.), the Ludwig Institute for Cancer Research (A.A.A.), NIH grant 1K99CA187192-01A1 (A.M.N.), NIH grant PHS NRSA 5T32 CA09302-35 (A.M.N.), US Department of Defense grant W81XWH-12-1-0498 (A.M.N.), a grant from the Siebel Stem Cell Institute and the Thomas and Stacey Siebel Foundation (A.M.N.), an NIH/Stanford MSTP training grant (B.C.), and a PD Soros Fellowship (B.C.).

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Correspondence to Aaron M. Newman or Ash A. Alizadeh .

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Chen, B., Khodadoust, M.S., Liu, C.L., Newman, A.M., Alizadeh, A.A. (2018). Profiling Tumor Infiltrating Immune Cells with CIBERSORT. In: von Stechow, L. (eds) Cancer Systems Biology. Methods in Molecular Biology, vol 1711. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7493-1_12

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  • DOI: https://doi.org/10.1007/978-1-4939-7493-1_12

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