Platelet Transcriptomic Profiling Identifies Resistance-Associated Signatures Among Patients With Non-Small Cell Lung Cancer Treated With Pembrolizumab-Based Regimens
According to findings from a translational study, platelet gene expression profiling has identified key molecular markers associated with resistance to first-line immunotherapy-based regimens in patients with advanced non-small cell lung cancer (NSCLC).
These findings were presented by Simona Coco, PhD, IRCCS Ospedale Policlinico San Martino, Genova, Italy, at the 2025 International Society of Liquid Biopsy (ISLB) Annual Meeting in Orlando, Florida.
In this study, researchers collected platelets at baseline and disease progression from the peripheral blood of 50 patients receiving first-line pembrolizumab either alone (n = 22) or in combination with chemotherapy (n = 28). Using serial centrifugation, platelets were isolated, then purity and activation status were confirmed using flow cytometry with antibodies against CD31 and CD42a, CD62p, and CD235. The NanoString PanCancer Immune Profiling panel was used for gene expression profiling to assess transcriptomic changes between baseline and progression.
At analysis, the platelet to lymphocyte ratio showed a significant upward trend from baseline to disease progression (P = .0065). Flow cytometry confirmed high platelet purity (CD31⁺/CD42a⁺), 0.3% erythrocyte contamination, and an activated platelet fraction of approximately 30%. Transcriptomic analyses revealed that 85 genes were upregulated at progression in the pembrolizumab monotherapy arm and 9 genes were upregulated at progression in the pembrolizumab plus chemotherapy arm. In the entire cohort, 58 genes were significantly overexpressed at progression including LAMP1, STAT3, CD40, CD63, LGALS3, and inhibitory immune markers CD99 and CD96.
“Platelet gene expression profiling led to the identification of key markers associated with resistance in patients treated with immunotherapy-based regimens, highlighting a potential role of [tumor-educated platelets]s in resistance mechanisms,” concluded Dr Coco. “Ongoing in vitro studies involving platelet-tumor cell co-cultures aim to elucidate the underlying pathway driving treatment resistance.”
Source:
Coco S. Platelet gene expression profiling as a liquid biopsy tool to monitor Immunotherapy resistance in advanced NSCLC patients. Presented at the 2025 ISLB Annual Meeting. November 1-3, 2025; Orlando, Florida. PP.08
