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Review
. 2020 May:131:40-50.
doi: 10.1016/j.ejca.2020.02.038. Epub 2020 Apr 9.

Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts

Jean-David Fumet  1 , Caroline Truntzer  2 , Mark Yarchoan  3 , Francois Ghiringhelli  4
Affiliations
Review

Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts

Jean-David Fumet et al. Eur J Cancer. 2020 May.

Abstract

Treatment with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) can generate durable responses in various cancer types, but only in a subset of patients. The use of predictive biomarkers for response to PD-1/PD-L1 inhibitors is critical for patient selection. Expression of PD-L1 has demonstrated utility in patient selection. Tumour mutational burden (TMB) is an emerging biomarker for response to PD-1/PD-L1 inhibitors. The evaluation of this biomarker is based on the hypothesis that a high number of mutations in somatic exonic regions will lead to an increase in neoantigen production, which could then be recognised by CD8+ T cells, resulting in improved immune responses. In this review, we will discuss rationale and implementation of TMB usage in patients, development of different methods to assess it, current limitations and technical issues to use this biomarker as a diagnostic test and propose future perspectives beyond TMB.

Keywords: Biomarker; Immunotherapy; Tumour mutational burden.

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Conflict of interest statement

Conflict of interest statement

All authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Mechanisms of Antigen (Ag) presentation.
Fig. 2.
Fig. 2.
Correlation between TMB, PDL1 expression and response rate to ICIs. A: correlation between TMB and overall response rate. B: correlation between PD-L1 and overall response rate. C: correlation between TMB and PD-L1.
Fig. 3.
Fig. 3.
Correlation between NGS panels and WES data to predict TMB.
Fig. 4.
Fig. 4.
Different biomarkers that could be combined to predict ICI efficacy.
See this image and copyright information in PMC

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