| 論文種別 | 原著(症例報告除く) |
| 言語種別 | 英語 |
| 査読の有無 | その他(不明) |
| 表題 | PD-L1 phenotype classification based on expression in tumor and immune cells as a potential biomarker for optimizing anti-PD-1/CTLA-4 immunotherapies in NSCLC. |
| 掲載誌名 | 正式名：Journal for immunotherapy of cancer 略 称：J Immunother Cancer ISSNコード：20511426/20511426 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 13(12),pp.e012880 |
| 著者・共著者 | Jun Miyakoshi, Tatsuya Yoshida, Yuji Uehara, Yuki Takeyasu, Masayuki Shirasawa, Akito Fukuda, Jumpei Kashima, Shogo Kumagai, Hidehito Horinouchi, Hanako Ono, Kouya Shiraishi, Takashi Kohno, Shunsuke Kondo, Yasushi Goto, Noboru Yamamoto, Yasushi Yatabe, Yukio Hosomi, Takayasu Kurata, Katsuhiko Naoki, Takuji Suzuki, Yuichiro Ohe |
| 発行年月 | 2025/12 |
| 概要 | BACKGROUND:Compared with conventional chemotherapy, pembrolizumab-based chemoimmunotherapy (Pembro) and nivolumab plus ipilimumab with or without two cycles of platinum-doublet chemotherapy (Nivo+Ipi) improve survival in advanced non-small cell lung cancer (NSCLC). However, biomarkers for selecting optimal immunotherapy remain unclear. This study aimed to assess whether programmed cell death-ligand 1 (PD-L1) expression on tumor and immune cells (ICs) can guide first-line immunotherapy in advanced NSCLC.METHODS:This multicenter, observational study retrospectively reviewed patients with NSCLC treated with first-line Pembro or Nivo+Ipi who had evaluable PD-L1 expression on tumor (Tumor Proportion Score (TPS), 22C3) and ICs score (SP142). In addition, whole-exome and RNA sequencing were performed on treatment-naïve NSCLCs with available PD-L1 expression status by both assays.RESULTS:Between 2019 and 2023, 198 patients were included (Pembro/Nivo+Ipi: 137/61). In the Pembro cohort, patients with high TPS (≥ 50%) had significantly longer progression-free survival (PFS) than those with low TPS (< 50%) (median PFS (mPFS, months): 8.1 vs 7.1; p=0.02), while IC score was not predictive. In the Nivo+Ipi cohort, high IC score (≥1) was associated with longer PFS than low IC score (0) (mPFS: 7.7 vs 2.8; p=0.04), while TPS showed no impact. Among patients with low TPS/high IC scores, Nivo+Ipi achieved longer PFS than Pembro (mPFS: 12.4 vs 6.6; restricted mean survival time (RMST)Nivo+Ipi/RMSTPembro (24 months)=1.5; p=0.049). Multiomics analysis using 152 NSCLC samples showed that tumors with low TPS/high IC scores exhibited an activated tumor immune microenvironment comparable to that of tumors with high TPS. However, these tumors had significantly highest tumor mutation burden (TMB) and regulatory T cell (Treg) fraction among the PD-L1 phenotypes (median TMB (mut/Mb): 1.6 in tumors with low TPS/low IC score, 18.2 in low TPS/high IC score, and 1.9 in high TPS/any IC score; median Treg fraction (×10-2]: 0.0, 0.2, and 0.0, respectively), supporting a potential benefit of cytotoxic T-lymphocyte-associated antigen 4 blockade in addition to programmed cell death protein 1 (PD-1)/PD-L1 inhibition in this subgroup.CONCLUSIONS:Patients with NSCLC and low TPS/high IC scores may benefit more from Nivo+Ipi than from Pembro due to distinct genomic and immunological features, including high TMB and Treg fraction. |
| DOI | 10.1136/jitc-2025-012880 |
| PMID | 41360425 |