Identification of inflamed-phenotype of small cell lung cancer leading to the efficacy of anti-PD-L1 antibody and chemotherapy. (May 2023)

• Record Type: Journal Article
• Authors: Shirasawa, Masayuki; Yoshida, Tatsuya; Shiraishi, Kouya; Takigami, Ayako; Takayanagi, Daisuke; Imabayashi, Tatsuya; Matsumoto, Yuji; Masuda, Ken; Shinno, Yuki; Okuma, Yusuke; Goto, Yasushi; Horinouchi, Hidehito; Yotsukura, Masaya; Yoshida, Yukihiro; Nakagawa, Kazuo; Tsuchida, Takaaki; Hamamoto, Ryuji; Yamamoto, Noboru; Motoi, Noriko; Kohno, Takashi; Watanabe, Shun-ichi; Ohe, Yuichiro
• Is Part Of: Lung cancer. Volume 179(2023)
• Publication Date: 2023-05
• Subjects: Small cell lung cancer (SCLC) -- Tumor-infiltrating lymphocyte (TIL) -- SCLC subtypes -- Platinum etoposide (ETP) plus programmed cell death ligand-1 (PD-L1) antibody therapy; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2023.107183
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: 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 . Abstract: Background: 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. Methods: 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. Results: 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). Conclusion: 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.