AUTHOR=Liu Yuqian , Wang Shenjie , Wang Yixuan , Li Yifei , Zhu Xiaoyan , Lai Xin , Zhang Xuanping , Li Xuqi , Xiao Xiao , Wang Jiayin TITLE=What makes TMB an ambivalent biomarker for immunotherapy? A subtle mismatch between the sample-based design of variant callers and real clinical cohort JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1151224 DOI=10.3389/fimmu.2023.1151224 ISSN=1664-3224 ABSTRACT=

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.