Cutting-Edge Platforms for Analysis of Immune Cells in the Hepatic Microenvironment—Focus on Tumor-Associated Macrophages in Hepatocellular Carcinoma

Daniel E. Millian, Omar A. Saldarriaga, Timothy Wanninger, Jared K. Burks, Yousef N. Rafati, Joseph Gosnell, Heather L. Stevenson

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

The role of tumor-associated macrophages (TAMs) in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. Most studies rely on platforms that remove intrahepatic macrophages from the microenvironment prior to evaluation. Cell isolation causes activation and phenotypic changes that may not represent their actual biology and function in situ. State-of-the-art methods provides new strategies to study TAMs without losing the context of tissue architecture and spatial relationship with neighboring cells. These technologies, such as multispectral imaging (e.g., Vectra Polaris), mass cytometry by time-of-flight (e.g., Fluidigm CyTOF), cycling of fluo-rochromes (e.g., Akoya Biosciences CODEX/PhenoCycler-Fusion, Bruker Canopy, Lunaphore Comet, and CyCIF) and digital spatial profiling or transcriptomics (e.g., GeoMx or Visium, Vizgen Merscope) are being utilized to accurately assess the complex cellular network within the tissue microenvi-ronment. In cancer research, these platforms enable characterization of immune cell phenotypes and expression of potential therapeutic targets, such as PDL-1 and CTLA-4. Newer spatial profiling platforms allow for detection of numerous protein targets, in combination with whole transcriptome analysis, in a single liver biopsy tissue section. Macrophages can also be specifically targeted and analyzed, enabling quantification of both protein and gene expression within specific cell phenotypes, including TAMs. This review describes the workflow of each platform, summarizes recent research using these approaches, and explains the advantages and limitations of each.

Original languageEnglish (US)
Article number1861
JournalCancers
Volume14
Issue number8
DOIs
StatePublished - Apr 1 2022

Keywords

  • CyTOF
  • HCC
  • TAMs
  • TME
  • cancer
  • hepatic microenvironment
  • liver
  • macrophages
  • scRNA-seq
  • spatial genomics
  • spectral imaging

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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