Plasma Proteomic Test Detects Immunotherapy Resistance Before Imaging in Lung Cancer

In advanced non-small cell lung cancer, monitoring response to immune checkpoint inhibitor therapy can be difficult when resistance develops before progression appears on imaging. Radiologic assessment remains a key reference for disease status, but earlier biological signals could provide additional insight during treatment. To identify such signals, researchers investigated whether longitudinal plasma proteomics can detect immunotherapy resistance before radiologic progression.

OncoHost is presenting research evaluating a 22-protein plasma signature designed to monitor treatment response over time in advanced non-small cell lung cancer. The approach uses longitudinal plasma proteomic profiling of serial blood samples collected during immune checkpoint inhibitor therapy. Changes in circulating protein patterns were analyzed to reflect treatment response, emerging resistance, and clinical outcomes.

The study analyzed 440 serial plasma samples from 109 patients with advanced non-small cell lung cancer across two independent cohorts. Patients received immune checkpoint inhibitor monotherapy, immune checkpoint inhibitors combined with chemotherapy, or dual immune checkpoint inhibitor therapy. Researchers assessed the association between the 22-protein signature and radiologic response according to Response Evaluation Criteria in Solid Tumors (RECIST), while also examining longitudinal proteomic patterns and overall survival.

The proteomic score was significantly associated with radiologic response in both cohorts and across the monotherapy and chemo-immunotherapy groups. Among patients who developed acquired resistance, proteomic score-based progression was detected a median of 170 days, or approximately 5.6 months, before progression was identified radiologically. 

Increasing or decrease-then-increase score patterns, consistent with primary and acquired resistance, were observed in 72% of patients who developed progressive disease. In contrast, decreasing proteomic scores were associated with significantly longer overall survival compared with increasing, decrease-then-increase, or stable trajectories.

The findings are being presented at the International Society of Liquid Biopsy meeting, taking place November 7–9 in Madrid, Spain. The abstract is titled “Longitudinal plasma proteomic profiling predicts immunotherapy response dynamics and overall survival (OS) in NSCLC.” The findings remain investigational, and further prospective validation is required to establish the clinical utility of the longitudinal monitoring signature.

“Plasma proteomics offers a unique opportunity to monitor the biological changes that occur throughout cancer treatment. Our findings demonstrate that longitudinal protein signatures can reflect treatment response, identify emerging resistance, and provide clinically meaningful information beyond conventional imaging. This brings us closer to using a blood test to continuously assess how patients are responding to therapy,” said Michal Harel, Ph.D., VP Translational Medicine at OncoHost.

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