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

Autor: Yuqian Liu, Shenjie Wang, Yixuan Wang, Yifei Li, Xiaoyan Zhu, Xin Lai, Xuanping Zhang, Xuqi Li, Xiao Xiao, Jiayin Wang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Immunology, Vol 14 (2023)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2023.1151224
Popis: 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.
Databáze: Directory of Open Access Journals