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Updated: Jun 16, 2026

Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
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Pan-cancer 8q24 amplification predicts primary immunotherapy resistance and therapeutic vulnerabilities

Changyuan Chen1, Shuye Liu1, Jingxiu Feng1

  • 1Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China.

Iscience
|June 15, 2026
PubMed

Insights

Chromosomal region 8q24 amplification in tumors creates an immune-depleted environment, predicting resistance to cancer immunotherapy. This finding offers a new biomarker for identifying non-responders and developing targeted therapies.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Immune checkpoint blockade revolutionized cancer treatment but lacks predictive biomarkers for non-responders.
  • Chromosomal region 8q24.21 amplification is common in cancers, yet its impact on anti-tumor immunity is unclear.

Purpose of the Study:

  • To investigate the role of 8q24 amplification in anti-tumor immunity and its association with immunotherapy response.
  • To identify 8q24 amplification as a predictive biomarker for immunotherapy resistance.

Main Methods:

  • Pan-cancer genomic profiling of 10,809 tumor samples.
  • Validation in five independent immunotherapy cohorts (over 800 patients).
  • Analysis of immune microenvironment, T cell infiltration, and antigen presentation.

Main Results:

  • 8q24 amplification found in ~10% of human cancers, associated with an immune-depleted microenvironment.
  • Reduced T cell infiltration and impaired antigen presentation observed in tumors with 8q24 amplification.
  • 8q24 amplification robustly predicted primary immunotherapy resistance and poor survival.

Conclusions:

  • 8q24 amplification serves as a predictive biomarker for immunotherapy resistance.
  • A composite score including 8q24 status, tumor mutational burden, and PD-L1 expression identifies non-responders.
  • Identified 8q24-specific vulnerabilities for targeted combination therapies in a defined patient subset.
Keywords:
cancertherapeutics

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