ONCOmmunity

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

By: Masayuki Shirasawa, Tatsuya Yoshida, Kouya Shiraishi, Ayako Takigami, Daisuke Takayanagi, Tatsuya Imabayashi, Yuji Matsumoto, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Masaya Yotsukura, Yukihiro Yoshida, Kazuo Nakagawa, Takaaki Tsuchida, Ryuji Hamamoto, Noboru Yamamoto, Noriko Motoi, Takashi Kohno, Shun-Ichi Watanabe, Yuichiro Ohe

Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara city, Kanagawa, 252-0375, Japan.
2022-11-24; doi: 10.1016/j.lungcan.2023.107183

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 TIL_High patients was significantly longer than that of TIL_Low 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.