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Updated: Jun 26, 2025

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer

Kyung-Pil Ko1, Shengzhe Zhang1, Yuanjian Huang1

  • 1Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Iscience
|May 14, 2024
PubMed

Insights

This study identifies distinct esophageal squamous cell cancer (ESCC) subtypes by analyzing the tumor microenvironment (TME). These subtypes help predict patient response to immune checkpoint inhibitors (ICIs), aiding treatment selection.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Immune checkpoint inhibitors (ICIs) show promise in cancer treatment, but resistance remains a significant challenge.
  • Patient selection is critical for optimizing ICI efficacy in esophageal squamous cell cancer (ESCC).

Purpose of the Study:

  • To subtype ESCC based on tumor microenvironment (TME) single-cell transcriptomic data.
  • To identify biomarkers for predicting ICI response in ESCC patients.

Main Methods:

  • Curated single-cell transcriptomic datasets from 69 human ESCC patients.
  • Performed integrative analyses of cellular networks and transcriptional signatures of T cells and myeloid cells.
  • Validated findings using whole tumor transcriptomes and liquid biopsy data.

Main Results:

  • Defined distinct ESCC subtypes characterized by T cell exhaustion and specific signaling pathways (IL and IFN).
  • Successfully classified ESCC patients into ICI responders and non-responders.
  • Demonstrated the predictive power of TME transcriptional networks for ICI response.

Conclusions:

  • Stratification of ESCC patients based on TME transcriptional networks offers novel insights into tumor niche remodeling.
  • This approach has the potential to predict ICI responses in ESCC, improving therapeutic strategies.
Keywords:
CancerCancer systems biologyImmune responseTranscriptomics

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