Dataset Information

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

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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7397649 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chen Yanhui Y Wang Yating Y Luo Hongli H Meng Xue X Zhu Wei W Wang Di D Zeng Hui H Zhang Henghui H

Experimental hematology & oncology 20200803

<h4>Background</h4>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.<h4>Methods</h4>PD-L1 expression, TMB, and PD-1<sup>+</sup> Tils (tumour-infiltrating lymphocytes) infiltration and their relationships were assessed in 6668 advanced solid tumour specimens across 25 tumour types. CD8<sup>+</ ...[more]

PMID: 32775040

Similar Datasets

Project description:BackgroundThe prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.ObjectivesThis study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.DesignThis real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018).MethodsTMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records.ResultsIn 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range, 0-46.83). Forty-eight patients (12%) had TMB ⩾10 mutations/Mb, 90% of which were B-cell or T-cell NHL. In 85 samples with available PD-L1 scores, 11 were high; 26, low; and 48, no tumor cell expression. PD-L1 TPS positive (⩾1%) was most common in T-cell NHL (7/9 (77%) cases) followed by B-cell NHL (21/51 (41%) cases). TMB ⩾4 mutations/Mb and PD-L1 score ⩾1% were significantly associated with shorter overall survival (OS) from diagnosis, with hazard ratio (HR) = 1.46 (p = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 (p = 0.04, 95% CI 1.04-4.30), respectively; the relationship was more pronounced when PD-L1 ⩾50% versus <50% was used (HR = 2.80, p = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient R 2 = 0.04, p = 0.04).ConclusionTMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies.Trial registrationClinicalTrials.gov NCT02478931.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets