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David S. Ettinger, MD, FACP, FCCP


SITC 2022: Use of Cell-Free DNA Monitoring to Predict Outcomes With Immunotherapy in NSCLC

By: Amy MacDonald, MS
Posted: Wednesday, November 16, 2022

Gulfem Guler, PhD, of Bluestar Genomics, San Mateo, California, presented data on behalf of his colleagues at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 7) on the use of 5-hydroxymethyl-cytosine (5hmC) signatures obtained from plasma-derived cell-free DNA to inform treatment decisions in patients receiving immunotherapy for non–small cell lung cancer (NSCLC). These preliminary study findings suggest that 5hmC profiling may provide putative patient selection biomarkers from blood in this patient population.

Binding between immune cell–expressed PD-1 and PD-1L on tumor cells is one mechanism by which tumor cells evade immune detection. Recent approval of anti–PD-1 agents has resulted in new therapeutic options for patients with NSCLC. However, not all patients with NSCLC respond to anti–PD-1 checkpoint inhibitors, and currently available biomarkers are insufficient to explain why.

Whole-blood samples were collected from 31 patients with NSCLC both prior to therapy and at up to five time points during anti–PD-1 therapy. Cell-free DNA was extracted from plasma and enriched using 5hmC-based epigenomic platform technology.

Anti–PD-1 treatment induced distinct changes in hydroxymethylomes in both responding and nonresponding patients with NSCLC. Following anti–PD1 treatment, 5hmC further accumulated over genes involved in immune activation alone in responding patients. Conversely, nonresponding patients’ cell-free DNA showed 5hmC increase over genes associated with metastasis and drug resistance. The pathway-based changes in responders and nonresponders were consistent with previous data from analysis of tumor tissue.

“Our results demonstrate that 5hmC profiling can capture tumor-associated immune response signals in plasma without the need for tissue biopsy,” the study authors concluded.

Disclosure: Dr. Guler is an employee of Bluestar Genomics.

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