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

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.

• Authors: 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
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 179 Pg. 107183 (05 2023) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 37037178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Etoposide

Topics

• Humans
• Small Cell Lung Carcinoma (drug therapy)
• Lung Neoplasms (drug therapy)
• Etoposide (therapeutic use)
• Retrospective Studies
• Phenotype