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

Exp Hematol Oncol. 2020 Aug 3;9:17. doi: 10.1186/s40164-020-00173-3. eCollection 2020.

Abstract

Background: PD-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.

Methods: PD-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.

Results: PD-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.

Conclusions: Our 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.

Keywords: Immunotherapy; PD-1; PD-L1; Solid tumour; TMB.