Journal for immunotherapy of cancer · 2025
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.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miyakoshi Jun, Yoshida Tatsuya, Uehara Yuji, Takeyasu Yuki, Shirasawa Masayuki, Fukuda Akito, Kashima Jumpei, Kumagai Shogo, Horinouchi Hidehito, Ono Hanako, Shiraishi Kouya, Kohno Takashi, Kondo Shunsuke, Goto Yasushi, Yamamoto Noboru, Yatabe Yasushi, Hosomi Yukio, Kurata Takayasu, Naoki Katsuhiko, Suzuki Takuji, Ohe Yuichiro
Аннотация
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.
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.