miRNA-Based Blood Borne Diagnostic Test Holds Potential for Management of Cancer Patients

By LabMedica International staff writers
Posted on 01 Apr 2022

Biomarkers have been shown to help identify cancer patients who are most likely to benefit from treatment with immunotherapies, such as PD-1/PD-L1-targeted therapies. Still, the gold standard of tumor tissue PD-L1 staining, as well as other biomarkers, such as tumor mutational burden, do not always accurately predict the efficacy of these therapies in cancer patients. Now, a first-of-its-kind microRNA (miRNA) biomarker signature offers the prospect of a blood-based companion diagnostic for immunotherapy in advanced non-small cell lung cancer (NSCLC).

Hummingbird Diagnostics GmbH (Heidelberg, Germany) is developing novel miRNA-based blood borne diagnostics for early disease detection of a broad range of indications. Immune cell-derived miRNAs reflect physiological and pathophysiological processes and can be sampled from peripheral blood. miRNAs are short non-coding RNAs that act as molecular rheostats that exercise control over the expression of most human genes. miRNAs are relatively accessible yet reflect complex underlying biology, offering the prospect of a blood-based companion diagnostic to determine the best candidates for immunotherapy. A recently published study led by Hummingbird describes the discovery and validation of a five-microRNA risk score (miRisk), illustrating the development of miRisk and its prognostic value for overall survival following immunotherapy. The blood-based test holds the potential for broad applicability for the management of patients with cancer.


Image: Blood-based microRNA analysis could predict overall survival for advanced NSCLC (Photo courtesy of Unsplash)

Based on an analysis of whole blood miRNA profiling of three well-characterized cohorts consisting of a total of 334 stage IV NSCLC patients, the researchers discovered and validated miRisk that is prognostic of overall survival following immunotherapy of either pembrolizumab or nivolumab. In a head-to-head comparison of miRisk and the gold standard PD-L1 tumor proportion score (TPS), the researchers found the diagnostic performance of miRisk to be superior as compared to PD-L1 status. Of note, the miRNA signature does not require tumor tissue and could thus be employed in an off-the-shelf manner.

The identified biomarker signature was traced back to a myeloid origin, especially neutrophils and macrophages, and miRNA target prediction was performed to identify a potential direct mechanistic link to the PD-L1 signaling pathway and PD-L1 itself. One example of a potential first clinical application is the selection of PD-L1-high patients for either single agent immunotherapy or chemo-immuno combination therapy where presently both options are licensed. In addition, miRisk measurements might provide a tissue-independent way of identifying by current standards ineligible patients who may benefit from immuno-monotherapy.

“Immunotherapy has revolutionized the treatment of non-oncogene-driven advanced cancers, yet only approximately 30% of patients respond favorably to these treatments. Determining which patients will respond to these powerful therapies represents one of the greatest needs in oncology,” said Bruno Steinkraus, PhD, Chief Scientific Officer of Hummingbird Diagnostics and leader of the published research. “This study illustrates the potential of how miRNAs taken from peripheral whole blood can be analyzed to predict the efficacy of PD-(L)1-targeted therapies in patients with NSCLC and improve patient outcomes.”

“Patient stratification - identifying who will benefit from treatment and who will likely fail to respond or even come to harm due to adverse events - remains challenging, and there is pressing need for more accurate biomarkers for immunotherapy response prediction,” said Jochen Kohlhaas, Founder and Chief Executive Officer of Hummingbird Diagnostics. “This work could broaden our general understanding of tumor immunobiology and, if validated, offers several important opportunities to improve management and outcomes of patients with advanced NSCLC and possibly other cancers.”

Related Links:
Hummingbird Diagnostics GmbH


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