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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Related Experiment Video

Updated: May 31, 2025

Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV
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Transcriptomic Profiling and Tumor Microenvironment Classification Reveal Unique and Dynamic Immune Biology in

Jihua Yang1, Ayse Ece Cali Daylan1, Aleksei Shevkoplias2

  • 1Department of Oncology (Medical Oncology), Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Cells
|January 24, 2025
PubMed
Summary

This study reveals distinct tumor microenvironments in Kaposi Sarcoma (KS) that vary by HIV status. Findings suggest a common antigen targeted by T cells, offering potential for new KS therapies.

Keywords:
HIVKaposi sarcomaTCR clonotypegene signaturesimmune milieutranscriptomicstumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Virology

Background:

  • Kaposi Sarcoma (KS) is a vascular tumor associated with human herpesvirus 8 (KSHV), disproportionately affecting underserved populations.
  • Antiretroviral therapy (ART) has improved outcomes for people with HIV (PWH), but advanced KS treatment remains challenging.

Purpose of the Study:

  • To investigate the tumor microenvironment (TME) of Kaposi Sarcoma (KS) using whole-transcriptomic profiling.
  • To analyze dynamic TME changes over time and differences based on HIV status in KS patients.

Main Methods:

  • Whole-transcriptomic profiling of KS tumor samples from nine patients (four HIV-negative, five HIV-positive).
  • Longitudinal sampling from three patients to track dynamic TME changes.
  • Immune cellular composition analysis using deconvolution, compared to non-KS tissues.

Main Results:

  • All KS samples showed enrichment in endothelial cells; KS tissues had higher percentages of NK and CD8+ T cells compared to non-KS tissues.
  • HIV-negative KS samples exhibited immune-enriched (IE) and immune-enriched/fibrotic (IE/F) TME subtypes; HIV-positive samples showed IE, IE/F, and fibrotic (F) subtypes.
  • A shared TCRβ chain was identified across all patients, indicating a T-cell response to a common antigen.

Conclusions:

  • Kaposi Sarcoma exhibits unique transcriptomic features and TME subtypes that are influenced by HIV status.
  • Longitudinal analysis revealed dynamic changes in gene signatures and TME subtypes within individual patients.
  • The presence of a shared TCRβ chain suggests potential for targeted immunotherapies for KS.