Table 5.

Predictive biomarkers of ICIs in ES-SCLC

Biomarkers	Summary
PD-L1	In CASPIAN and IMPower study, PD-L1 expression had no significant correlation with OS. However, a meta-analysis indicated that positive PD-L1 expression demonstrated a trend towards longer OS.
TMB	In CheckMate 032 trial, Results indicated that the OS and PFS of high TMB group who received nivolumab or nivolumab plus ipilimumab were superior to medium TMB group and low TMB group which reminded us that SCLC patients with high TMB could obtain more survival benefits.
TIL and GEP	In the phase Ib Keynote 028 trial, the patient group with SCLC showed an ORR of 33% after treatment with pembrolizumab. The study showed that tumor T cell-inflamed GEPs were a potential predictive biomarker of pembrolizumab response.
CTC	The study of Tamminga, which involved 104 NSCLC patients received immunotherapy, showed patients with decreased CTC levels were more likely to benefit from immunotherapy.
Metastasis sites	In KEYNOTE-158 study, OS benefits wasn’t observed in patients with hepatic metastases compared to patients without metastases. In IMPower133 study, SCLC patients with brain metastases did not appear to benefit from ICI in combination with chemotherapy.

TMB: tumor mutation burden; TIL: tumor infiltrating lymphocyte; GEN: gene-expression profifile; CTC: circulating tumor cells.