The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China

Di Wang,Hongli Luo,Yating Wang,Hui Zeng,Yanhui Chen,Xue Meng,Wei Zhu,Henghui Zhang

doi:10.1186/s40164-020-00173-3

Abstract

BackgroundPD-L1 expression and tumour mutational burden (TMB) are both associated with the responses of multiple tumours to immune checkpoint inhibitor (ICI) therapy. However, their prevalence and correlations may differ in different types of advanced solid tumours.MethodsPD-L1 expression, TMB, and PD-1+ Tils (tumour-infiltrating lymphocytes) infiltration and their relationships were assessed in 6668 advanced solid tumour specimens across 25 tumour types. CD8+ T cell infiltration was analysed in 347 NSCLC samples. The associations of these biomarkers with the therapeutic effect of PD-1 inhibitor were analysed in a cohort of NSCLC samples.ResultsPD-L1 expression levels and TMB in different tumour types varied widely and their relationship was not significantly correlated in most cancer types, with only a small association across all specimens (Spearman R = 0.059). PD-1+ Tils infiltration was positively correlated with PD-L1 expression across all samples (Spearman R = 0.3056). However, there is no such correlation between PD-1+ Tils infiltration and TMB. In NSCLC samples, CD8+ T cell infiltration was correlated with PD-1+ Tils infiltration and PD-L1 expression but not with TMB (Spearman R = 0.4117, 0.2045, and 0.0007, respectively). Patients in the CR/PR group (anti-PD-1 therapy) had higher levels of PD-L1 expression, TMB, PD-1+ Tils, and CD8+ T cell infiltration, and many patients in this group exhibited concomitantly elevated levels of multiple biomarkers.ConclusionsOur results showed the PD-L1 expression status and TMB in various types of advanced solid tumours in Chinese patients and their relationships with PD-1+ Tils and CD8+ T cell infiltration, which may inform ICI treatment.

Highlights

Programmed death ligand-1 (PD-L1) expression and tumour mutational burden (TMB) are both associated with the responses of multiple tumours to immune checkpoint inhibitor (ICI) therapy
Progressive disease (PD)‐L1 expression and TMB landscape across tumour types In total, 6668 patients with advanced tumours representing 25 tumour types were enrolled in the study, and samples with paired PD-L1 expression and TMB value were obtained during the course of standard clinical care
Nasopharyngeal carcinoma and thymic carcinoma had the highest frequency of PD-L1 positivity (75% and 68%, respectively), whereas small bowel carcinoma had the lowest frequency of PD-L1 positivity (9%, Fig. 1a)

Summary

Introduction

PD-L1 expression and tumour mutational burden (TMB) are both associated with the responses of multiple tumours to immune checkpoint inhibitor (ICI) therapy. Their prevalence and correlations may differ in different types of advanced solid tumours. A comprehensive analysis on the prevalence of PD-L1 expression and TMB and their relationship in different tumour types may enlighten the clinical practice of ICI therapies and help to more accurately select ICI responders. PD-L1, TMB, PD-1, and CD8 are each a potentially relevant link in the antitumour immune response process; their correlations have not been reported with large samples from multiple cancer types. The frequency and correlation of these biomarkers in different types of solid tumours from Chinese patients have not been reported in large sample sizes

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