Ohkuma Ryotaro, Fujimoto Yuki, Ieguchi Katsuaki, Onishi Nobuyuki, Watanabe Makoto, Takayanagi Daisuke, Goshima Tsubasa, Horiike Atsushi, Hamada Kazuyuki, Ariizumi Hirotsugu, Hirasawa Yuya, Ishiguro Tomoyuki, Suzuki Risako, Iriguchi Nana, Tsurui Toshiaki, Sasaki Yosuke, Homma Mayumi, Yamochi Toshiko, Yoshimura Kiyoshi, Tsuji Mayumi, Kiuchi Yuji, Kobayashi Shinichi, Tsunoda Takuya, Wada Satoshi
Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo 142-8555, Japan.
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo 157-8577, Japan.
Oncol Lett. 2023 Jul 20;26(3):381. doi: 10.3892/ol.2023.13967. eCollection 2023 Sep.
Immune checkpoint inhibitors (ICIs) are among the most notable advances in cancer immunotherapy; however, reliable biomarkers for the efficacy of ICIs are yet to be reported. Programmed death (PD)-ligand 1 (L1)-expressing CD14 monocytes are associated with shorter overall survival (OS) time in patients with cancer treated with anti-PD-1 antibodies. The present study focused on the classification of monocytes into three subsets: Classical, intermediate and non-classical. A total of 44 patients with different types of cancer treated with anti-PD-1 monotherapy (pembrolizumab or nivolumab) were enrolled in the present study. The percentage of each monocyte subset was investigated, and the percentage of cells expressing PD-L1 or PD-1 within each of the three subsets was further analyzed. Higher pretreatment classical monocyte percentages were correlated with shorter OS (r=-0.32; P=0.032), whereas higher non-classical monocyte percentages were correlated with a favorable OS (r=0.39; P=0.0083). PD-L1-expressing classical monocytes accounted for a higher percentage of the total monocytes than non-classical monocytes with PD-L1 expression. In patients with non-small cell lung cancer (NSCLC), a higher percentage of PD-L1-expressing classical monocytes was correlated with shorter OS (r=-0.60; P=0.012), which is similar to the observation for the whole patient cohort. Comparatively, higher percentages of non-classical monocytes expressing PD-L1 were significantly associated with better OS, especially in patients with NSCLC (r=0.60; P=0.010). Moreover, a higher percentage of non-classical monocytes contributed to prolonged progression-free survival in patients with NSCLC (r=0.50; P=0.042), with similar results for PD-L1-expressing non-classical monocytes. The results suggested that the percentage of monocyte subsets in patients with cancer before anti-PD-1 monotherapy may predict the treatment efficacy and prognosis. Furthermore, more classical monocytes and fewer non-classical monocytes, especially those expressing PD-L1, are involved in shortening OS time, which may indicate the poor efficiency of anti-PD-1 treatment approaches.
免疫检查点抑制剂（ICIs）是癌症免疫治疗中最显著的进展之一；然而，关于ICIs疗效的可靠生物标志物尚未见报道。表达程序性死亡（PD）配体1（L1）的CD14单核细胞与接受抗PD-1抗体治疗的癌症患者较短的总生存期（OS）相关。本研究聚焦于将单核细胞分为三个亚群：经典型、中间型和非经典型。本研究共纳入了44例接受抗PD-1单药治疗（派姆单抗或纳武单抗）的不同类型癌症患者。研究了每个单核细胞亚群的百分比，并进一步分析了三个亚群中表达PD-L1或PD-1的细胞百分比。治疗前经典单核细胞百分比越高，与OS越短相关（r=-0.32；P=0.032），而非经典单核细胞百分比越高，则与良好的OS相关（r=0.39；P=0.0083）。表达PD-L1的经典单核细胞在总单核细胞中所占的百分比高于表达PD-L1的非经典单核细胞。在非小细胞肺癌（NSCLC）患者中，表达PD-L1的经典单核细胞百分比越高，与OS越短相关（r=-0.60；P=0.012），这与整个患者队列的观察结果相似。相比之下，表达PD-L1的非经典单核细胞百分比越高，与更好的OS显著相关，尤其是在NSCLC患者中（r=0.60；P=0.010）。此外，较高比例的非经典单核细胞有助于NSCLC患者延长无进展生存期（r=0.50；P=0.042），表达PD-L1的非经典单核细胞也有类似结果。结果表明，抗PD-1单药治疗前癌症患者单核细胞亚群的百分比可能预测治疗疗效和预后。此外，更多的经典单核细胞和更少的非经典单核细胞，尤其是那些表达PD-L1的细胞，参与缩短OS时间，这可能表明抗PD-1治疗方法的效率低下。
