•In SCLC, it remains unclear what patients can benefit from the platinum etoposide plus PD-L1 antibody.•The LS-SCLC cohort was classified into four SCLC subtypes based on transcriptomic data.•SCLC-I showed enriched immune-related pathways, the highest immune score, and EMT.•IHC showed that SCLC-I had the highest density of CD8-positive TILs within the TME in transcriptional subtypes.•In ES-SCLC treated with the platinum etoposide plus anti-PD-L1 antibody, the PFS of patients with TILHigh was significantly better than those with TILLow. Platinum etoposide plus anti-programmed cell death ligand-1 (PD-L1) antibody therapy is the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, patient characteristics associated with the efficacy of the combination therapy in SCLC are unclear. We retrospectively reviewed post-surgical limited-stage (LS)-SCLC and ES-SCLC patients treated with atezolizumab plus carboplatin and etoposide (ACE). The association between SCLC subtypes based on transcriptomic data and pathological findings, including CD8-positive tumor-infiltrating lymphocyte (TIL) status, was investigated in the LS-SCLC cohort. The association between the efficacy of ACE therapy, pathological subtypes, and TIL status was evaluated in the ES-SCLC cohort. The LS-SCLC cohort (N = 48) was classified into four SCLC subtypes (ASCL1 + NEUROD1 SCLC-A + N, N = 17, POU2F3 SCLC-P, N = 15, YAP1 SCLC-Y, N = 10, and inflamed SCLC-I, N = 6) based on transcriptomic data. SCLC-I showed enriched immune-related pathways, the highest immune score (CD8A expression and T-cell–inflamed gene expression profiles), and epithelial–mesenchymal transition (EMT), in transcriptional subtypes. Immunohistochemical staining (IHC) showed that SCLC-I had the highest density of CD8-positive TILs in transcriptional subtypes. In the ES-SCLC cohort, the efficacy of ACE therapy did not differ according to pathological subtypes. The progression-free survival (PFS) of TILHigh patients was significantly longer than that of TILLow patients (PFS: 7.3 months vs. 4.0 months, p < 0.001). Tumors with a high density of TILs, which represent the most immunogenic SCLC subtype (SCLC-I), based on transcriptomic data could benefit from ACE therapy.