Molecular markers related to immunosurveillance as predictive and monitoring tools in non-small cell lung cancer: recent accomplishments and future promises

ABSTRACT

Introduction: The landscape of systemic treatment options for lung cancer has rapidly evolved with the emergence of immunomodulatory agents such as neutralizing antibodies targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Another major breakthrough was the introduction of biomarkers, such as PD-L1 expression and tumor mutational burden (TMB), predicting response to immunotherapy. However, markers for monitoring treatment response are still lacking.

Areas covered: PD-L1 and TMB represent static pre-treatment evaluations. Dynamic biomarkers are required, along with static ones, to accurately predict and monitor immunotherapy response and to discriminate between responders and non-responders early in the course of treatment. The tumor immune contexture offers potential candidates that can be tested through the liquid biopsy approach, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, microRNAs (miRNAs), circular RNAs (circRNAs), RNA splice variants, and immune cell subsets.

Expert opinion: A holistic approach combining information from tissue at the time of diagnosis and serial liquid biopsy data could lead to a novel combinatorial biomarker panel with enhanced treatment monitoring potential. Incorporating information from additional parts of the tumor-host ecosystem, such as metabolic markers and the microbiome is expected to provide added value to this strategy.

KEYWORDS:

• NSCLC
• immuno-oncology
• predictive biomarkers
• monitoring treatment response
• PD-1/PD-L1
• liquid biopsy

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.