Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in

Manuel Pino-González1, Martín Lázaro-Quintela1,2, Irene Alonso-Álvarez1

  • 1Translational Oncology Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Hospital Álvaro Cunqueiro, Carretera Clara Campoamor, 341, 36213, Vigo, Spain.

Scientific Reports
|November 20, 2025
PubMed

Insights

T-cell receptor (TCR) repertoire analysis shows promise as a predictive biomarker for immunotherapy response in advanced non-small cell lung cancer (NSCLC) patients treated with pembrolizumab.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Immunotherapy offers new treatment options for advanced non-small cell lung cancer (NSCLC).
  • Predicting patient response to immunotherapy remains a challenge due to the lack of effective biomarkers.
  • T cells are crucial for anti-tumor immunity, making T cell receptors (TCRs) potential predictive markers.

Purpose of the Study:

  • To evaluate the potential of baseline TCR repertoire as a predictive biomarker for immunotherapy response in advanced NSCLC patients.
  • To assess if TCR repertoire can predict response to first-line pembrolizumab treatment.

Main Methods:

  • Peripheral blood and tissue samples were collected at baseline from advanced NSCLC patients.
  • Next-generation sequencing was performed targeting TCRβ/γ genes.
  • Analysis of tumor-infiltrating and circulating TCR repertoires was conducted.

Main Results:

  • An uneven tumor-infiltrating TCRβ repertoire was observed.
  • Specific tumor-infiltrating and circulating TRBV/J gene usage predicted immunotherapy response.
  • Baseline TCR repertoire analysis demonstrated potential as a predictive biomarker.

Conclusions:

  • Evaluating tissue and circulating TCRβ repertoire before pembrolizumab treatment is supported.
  • TCR repertoire emerges as a promising biomarker for predicting immunotherapy response in NSCLC patients.

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