Longitudinal plasma proteomic profiling of patients with non-small cell lung cancer undergoing immune checkpoint blockade.
J Immunother Cancer
; 10(6)2022 06.
Article
em En
| MEDLINE
| ID: mdl-35718373
ABSTRACT
BACKGROUND:
Immune checkpoint inhibitors (ICIs) have revolutionized the cancer therapy landscape due to long-term benefits in patients with advanced metastatic disease. However, robust predictive biomarkers for response are still lacking and treatment resistance is not fully understood.METHODS:
We profiled approximately 800 pre-treatment and on-treatment plasma proteins from 143 ICI-treated patients with non-small cell lung cancer (NSCLC) using ELISA-based arrays. Different clinical parameters were collected from the patients including specific mutations, smoking habits, and body mass index, among others. Machine learning algorithms were used to identify a predictive signature for response. Bioinformatics tools were used for the identification of patient subtypes and analysis of differentially expressed proteins and pathways in each response group.RESULTS:
We identified a predictive signature for response to treatment comprizing two proteins (CXCL8 and CXCL10) and two clinical parameters (age and sex). Bioinformatic analysis of the proteomic profiles identified three distinct patient clusters that correlated with multiple parameters such as response, sex and TNM (tumors, nodes, and metastasis) staging. Patients who did not benefit from ICI therapy exhibited significantly higher plasma levels of several proteins on-treatment, and enrichment in neutrophil-related proteins.CONCLUSIONS:
Our study reveals potential biomarkers in blood plasma for predicting response to ICI therapy in patients with NSCLC and sheds light on mechanisms underlying therapy resistance.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_other_respiratory_diseases
/
6_trachea_bronchus_lung_cancer
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Antineoplásicos Imunológicos
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunother Cancer
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Israel