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<p>Immunotherapy has opened new avenues of treatment for patients with advanced non-small cell lung cancer (NSCLC) without previous hope of survival. Unfortunately, only a small percentage of patients benefit from it and there is not an effective biomarker to predict patients’ response. Since T cells are key effectors of antitumor immunity, T cell receptor (TCR) has emerged as a potential predictive biomarker. Here, we evaluated the potential of baseline TCR repertoire, as a predictive biomarker in advanced NSCLC patients treated with pembrolizumab at first-line. After obtaining peripheral blood and tissue samples at baseline, next-generation sequencing targeting TCRβ/γ was performed. We found an uneven tumor-infiltrating TCRβ repertoire, and the use of various tumor-infiltrating and circulating TRBV/J genes were able of predicting the immunotherapy response. Our results support the potential of evaluating tissue and circulating TCRβ repertoire prior to pembrolizumab, revealing it as a promising immunotherapy response biomarker in NSCLC patients.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • Manuel Pino-González,
  • Martín Lázaro-Quintela,
  • Irene Alonso-Álvarez,
  • María Gallardo-Gómez,
  • Laura Juaneda-Magdalena,
  • Alejandro Francisco-Fernández,
  • Silvia Calabuig-Fariñas,
  • Eloisa Jantus-Lewintre,
  • Mónica Martínez-Fernández

摘要

Immunotherapy has opened new avenues of treatment for patients with advanced non-small cell lung cancer (NSCLC) without previous hope of survival. Unfortunately, only a small percentage of patients benefit from it and there is not an effective biomarker to predict patients’ response. Since T cells are key effectors of antitumor immunity, T cell receptor (TCR) has emerged as a potential predictive biomarker. Here, we evaluated the potential of baseline TCR repertoire, as a predictive biomarker in advanced NSCLC patients treated with pembrolizumab at first-line. After obtaining peripheral blood and tissue samples at baseline, next-generation sequencing targeting TCRβ/γ was performed. We found an uneven tumor-infiltrating TCRβ repertoire, and the use of various tumor-infiltrating and circulating TRBV/J genes were able of predicting the immunotherapy response. Our results support the potential of evaluating tissue and circulating TCRβ repertoire prior to pembrolizumab, revealing it as a promising immunotherapy response biomarker in NSCLC patients.