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

作者：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 · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2025-012880 · 被引用次数：2 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Immune cells in cancer

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+...