Highlights
- •Treatment with immune checkpoint inhibitors can generate durable responses but only in a subset of patients.
- •The use of predictive biomarkers is critical for patient selection.
- •Tumor mutational burden (TMB) is an emerging biomarker for response to PD-1/PD-L1 inhibitors.
- •Various strategies exists to assess it and present limitations and technical issues.
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
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Article info
Publication history
Published online: April 09, 2020
Accepted:
February 13,
2020
Received:
December 20,
2019
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
