Immune checkpoint blockade as a potential therapeutic target in non-small cell lung cancer

ABSTRACT

Introduction: The recent emergence of immune checkpoint blockade therapy and the progression of immunobiology in cancer have spurred an increasing interest in the immunotherapy for advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs), designed to directly target immune inhibitory molecules, have demonstrated efficacy in the treatment of patients with advanced NSCLC.

Areas covered: In the present article, the authors summarize the mechanism, efficacy and safety of major ICIs for the treatment of advanced or metastatic NSCLC. Combinations of different ICIs or conventional therapy and/or targeted agents for NSCLC treatment in clinical trials are also updated. In addition, immune-related adverse events and the roles of inhibitory immune checkpoint molecules as potential biomarkers in the immune checkpoint blockade therapy for NSCLC are emphatically elucidated.

Expert opinion: Immunotherapies targeting the immune checkpoint pathways have shown potential to generate durable responses and improve survival for NSCLC patients. Although the toxicity profile of this immunotherapy is manageable, immune-related adverse events and drug resistance may cause therapeutic failure. Therefore, a better understanding of the mechanisms underpinning its function and the potential side effects of ICIs, as well as the identification of predictive biomarkers for patient selection are essential.

KEYWORDS:

• Cytotoxic T-lymphocyte-associated protein 4
• immune checkpoint inhibitor
• non-small cell lung cancer
• programmed cell death protein 1
• programmed cell death protein ligand-1

Article highlights

• Immune checkpoint blockade therapy is a promising treatment for many cancer types, including non-small cell lung cancer (NSCLC).

• Immune checkpoint inhibitors targeting the PD-1/PD-L1 and CTLA-4 immune regulatory pathways exhibit potentials to generate responses in patients with NSCLC in clinical settings.

• The U.S. Food and Drug Administration and the European Medicines Agency have recently approved the use of several immune checkpoint inhibitors in NSCLC treatment.

• Clinical studies on the safety and efficacy of immune checkpoint blockades as monotherapy or combined therapeutic strategies in NSCLC treatment are ongoing.

• A better understanding in the mechanisms of functions, potential immune-related adverse events and the identification of predictive biomarkers for patient selection may lead to an improvement in the management and clinical efficacy of immune checkpoint blockade therapy for NSCLC treatment.

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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.

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Additional information

Funding

This work is supported by grants from the National Natural Science Foundation of China [Nos. 31472191 and 81460247].