Advances in biomarkers for immunotherapy in small-cell lung cancer.

Small-cell lung cancer (SCLC) is a refractory cancer with rapid growth and high aggressiveness. Extensive-stage SCLC is initially sensitive to chemotherapy; however, drug resistance and recurrence occur rapidly, resulting in a poor survival outcome due to lack of subsequently efficient therapy. The emergence of immune checkpoint inhibitors (ICIs) generated a new landscape of SCLC treatment and significantly prolonged the survival of patients. However, the unselected immunotherapy restrains both beneficiary population and responsive period in SCLC compared to the other tumors. The complex tumor origin, high heterogeneity, and immunosuppressive microenvironment may disturb the value of conventional biomarkers in SCLC including programmed cell death 1 ligand 1 and tumor mutation burden. Transcriptional regulator-based subtypes of SCLC are current research hotspot, revealing that Y (I) subtype can benefit from ICIs. Additionally, molecules related to immune microenvironment, immunogenicity, epigenetics, and SCLC itself also indicated the therapeutic benefits of ICIs, becoming potential predictive biomarkers. In this review, we discussed the advances of biomarkers for prediction and prognosis of immunotherapy, promising directions in the future, and provide reference and options for precision immunotherapy and survival improvement in patients with SCLC.