Abstract
BACKGROUND: Small cell lung cancer (SCLC) accounts for about 13-15% of all lung cancers, and about 70% of SCLC patients have developed extensive-stage small cell lung cancer (ES-SCLC) at the time of diagnosis because of its highgrade malignancy, easy invasion, and metastasis. In recent years, immunotherapy combined with chemotherapy has become the standard first-line treatment for ES-SCLC. However, SCLC is a relatively immune-cold lung cancer subtype with a limited number of beneficiaries and a short benefit period. Therefore, the use of biomarkers to identify populations with significant benefits from immunotherapy will help improve the efficacy and survival benefits of immunotherapy. However, predictive biomarkers suitable for clinical practice have not been established in the field of SCLC. PURPOSE: In order to find the predictive biomarkers of immunotherapy for ES-SCLC, we summarized the research progress of traditional biomarkers, such as programmed cell death ligand 1 (PD-L1) and tumor mutation burden (TMB), and summarizes the research of potential biomarkers associated with prognosis, such as molecular subtypes, special gene expression, expression of major histocompatibility complex (MHC) I and II classes, tumor immune microenvironment (TIME), and circulating tumor DNA (ctDNA) .We aim to provide new insights on biomarkers. CONCLUSION: The exploration of biomarkers for immunotherapy of SCLC is still very difficult, and it is clear that conventional predictive biomarkers are not suitable for SCLC. At present, the molecular subtypes defined from transcription factors may have some guiding significance, which still needs to be confirmed by prospective clinical studies. In addition, the ctDNA positivity rate of SCLC is higher than that of other tumor types, which can also solve the dilemma of the difficulty of obtaining specimens of SCLC tissues. And the dynamic change of ctDNA also has great potential to predict the curative effect of SCLC, which is worth further clinical exploration.