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Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Updated: Jun 26, 2025

Predictive Immune Modeling of Solid Tumors
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Transcriptome Deconvolution Reveals Absence of Cancer Cell Expression Signature in Immune Checkpoint Blockade

Yu Amanda Guo1, Tanmay Kulshrestha1, Mei Mei Chang1

  • 1Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, #02-01 Genome, Singapore 138672, Republic of Singapore.

Cancer Research Communications
|May 9, 2024
PubMed
Summary
This summary is machine-generated.

Biomarkers for immune checkpoint therapy (ICB) response are crucial. This study found stromal cell gene expression, not cancer cell expression, predicts ICB outcomes, challenging current diagnostic approaches.

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Immune checkpoint therapy (ICB) offers significant benefits for some cancer patients, but response rates remain limited.
  • Identifying reliable biomarkers is essential for patient stratification and improving treatment efficacy.

Purpose of the Study:

  • To conduct a comprehensive transcriptome-wide meta-analysis to identify cell-type specific gene expression patterns associated with ICB response.
  • To investigate whether cancer cells or stromal cells harbor conserved transcriptomic features predictive of ICB outcomes across diverse cancer types.

Main Methods:

  • Performed a transcriptome-wide meta-analysis of 1,486 tumors from ICB-treated patients.
  • Utilized a robust transcriptome deconvolution approach to infer cancer- and stroma-specific gene expression.
  • Analyzed gene expression patterns in relation to ICB response and microsatellite status.

Main Results:

  • Stromal expression of CXCL9, CXCL13, and IFNG were key determinants of favorable ICB response.
  • Identified immune-suppressive genes like FCER1A associated with poor ICB response.
  • PD-L1 expression in stromal cells, not cancer cells, correlated with ICB response across cancer types.
  • No conserved cancer-cell intrinsic expression signatures predictive of ICB response were identified across tumor types.

Conclusions:

  • Cancer cells lack tissue-agnostic transcriptomic features that modulate ICB response.
  • Stromal cell gene expression is a critical determinant of ICB efficacy, challenging the focus on cancer-cell intrinsic markers.
  • Findings have significant implications for developing improved ICB diagnostics and therapeutic strategies.