Frontiers in Immunology (May 2023)

What makes TMB an ambivalent biomarker for immunotherapy? A subtle mismatch between the sample-based design of variant callers and real clinical cohort

  • Yuqian Liu,
  • Yuqian Liu,
  • Shenjie Wang,
  • Shenjie Wang,
  • Yixuan Wang,
  • Yifei Li,
  • Xiaoyan Zhu,
  • Xiaoyan Zhu,
  • Xin Lai,
  • Xin Lai,
  • Xuanping Zhang,
  • Xuanping Zhang,
  • Xuqi Li,
  • Xiao Xiao,
  • Xiao Xiao,
  • Jiayin Wang,
  • Jiayin Wang

DOI
https://doi.org/10.3389/fimmu.2023.1151224
Journal volume & issue
Vol. 14

Abstract

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Tumor mutation burden (TMB) is a widely recognized biomarker for predicting the efficacy of immunotherapy. However, its use still remains highly controversial. In this study, we examine the underlying causes of this controversy based on clinical needs. By tracing the source of the TMB errors and analyzing the design philosophy behind variant callers, we identify the conflict between the incompleteness of biostatistics rules and the variety of clinical samples as the critical issue that renders TMB an ambivalent biomarker. A series of experiments were conducted to illustrate the challenges of mutation detection in clinical practice. Additionally, we also discuss potential strategies for overcoming these conflict issues to enable the application of TMB in guiding decision-making in real clinical settings.

Keywords