A narrative review of current and potential prognostic biomarkers for immunotherapy in small-cell lung cancer

Small-cell lung cancer (SCLC) is a highly invasive and rapidly proliferating pathologic subtype that accounts for 13–15% of all lung cancer cases. Recently in extensive-stage SCLC, treatments that combine immunotherapy and chemotherapy showed increased efficacy compared to chemotherapy alone in several trials. However, the combination of immunotherapy and conventional chemotherapy regimens was introduced only recently for extensive-stage SCLC, with relatively little real-world data. The demand for reliable biomarkers that can predict the efficacy of immunotherapy in SCLC is high. Several studies evaluated various parameters including programmed cell death ligand-1 (PD-L1) expression, tumor mutation burden (TMB), gene expression profiling, autoantibody, and blood cytokines for predictive value for response to immunotherapy in SCLC. Despite some observed correlations, there is a lack of concrete support for the use of PD-L1 expression levels for readily available biomarker. High TMB in combination with smoking history is predictive of a better response to immunotherapy, but validation of cutoffs and testing methods is necessary before it can be widely applied in clinical settings. Other candidate biomarkers such as immune cell distribution among tumor microenvironment, and systemic inflammatory markers can also be evaluated, after an accumulation of real-life data from SCLC patients under immunotherapy.