KEY TAKEAWAYS
- The study aimed to analyze early on-treatment proteomic changes in blood plasma to enhance comprehension of treatment response and resistance.
- The results showed plasma proteomics’ potential in elucidating ICI therapy’s biological processes, indicating promise for therapy resistance mechanisms and outcome biomarkers.
While immune checkpoint inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment, heterogeneous clinical responses and inadequate predictive biomarkers persist.
Jair Bar and the team spearheaded the study that aimed to analyze early treatment-related proteomic alterations in blood plasma to enhance comprehension of treatment response and resistance.
Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample.
Further analysis was conducted on proteins displaying significant fold changes (T1:T0) to identify associations with clinical outcomes, including clinical benefit and overall survival (OS). Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.
The analysis revealed that following ICI-based treatments, NSCLC patients exhibited significantly increased levels of 142 proteins in their plasma. The soluble PD-1 showed the highest elevation, correlating positively with tumor PD-L1 status. In the ICI monotherapy dataset, it was also associated with improved OS.
The bioinformatic analysis of this dataset unveiled a network of 30 upregulated proteins, notably featuring CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Interestingly, this T cell-related network was detected irrespective of clinical benefit. Additionally, proteins originating from the alveoli were identified as potential biomarkers of limited clinical benefit, potentially linked to cellular stress and lung damage.
The study showed that ICI-based therapy activates biological processes, highlighting plasma proteomics’ potential to identify therapy resistance mechanisms and outcome biomarkers.
The study was supported by the OncoHost LTD.
Source: https://pubmed.ncbi.nlm.nih.gov/38487531/
Bar J, Leibowitz R, Reinmuth N, et al. (2024) “Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy.” Front Immunol. 2024 Feb 29;15:1364473. doi: 10.3389/fimmu.2024.1364473. PMID: 38487531; PMCID: PMC10937428.
