Moeller Ann, Kurzrock Razelle, Botta Gregory P, Adashek Jacob J, Patel Hitendra, Lee Suzanna, Pabla Sarabjot, Nesline Mary K, Conroy Jeffrey, Sicklick Jason K, Kato Shumei
Sharp Rees-Stealy Medical Group San Diego, CA, USA.
Medical College of Wisconsin Cancer Center and Genomic Sciences and Precision Medicine Center Milwaukee, WI, USA.
Am J Cancer Res. 2023 Jul 15;13(7):3257-3265. eCollection 2023.
CSF1R expression modulates tumor-associated macrophages, making CSF1R blockade an appealing immune-modulating therapeutic target. We evaluated the correlation between CSF1R tumor RNA expression and outcome (pan-cancer setting). RNA expression was ranked as a percentile (0-100) using a standardized internal reference population (735 tumors; 35 histologies). Among 514 patients, there was no difference in survival from biopsy between high and low CSF1R expressors (< 50 percentile versus ≥ 50 percentile rank). There was also no significant difference in median progression-free or overall survival (from treatment) based on CSF1R expression in 21 patients who received CSF1R inhibitors (all values ≥ 0.08). Concurrent upregulation of ≥ 2 additional immune checkpoint markers (e.g. PD-L1, BTLA, CTLA4, LAG3, TIM3) was observed in all tumor samples with CSF1R expression ≥ 50th percentile. Pending further large prospective studies, patients with high tumor CSF1R expression may need treatment that co-targets the specific immune checkpoint pathways activated in order to impact outcome.
集落刺激因子1受体（CSF1R）的表达可调节肿瘤相关巨噬细胞，这使得CSF1R阻断成为一个有吸引力的免疫调节治疗靶点。我们评估了CSF1R肿瘤RNA表达与预后之间的相关性（泛癌背景）。使用标准化的内部参考人群（735个肿瘤；35种组织学类型）将RNA表达按百分位数（0-100）进行排名。在514例患者中，CSF1R高表达者（百分位数<50与≥50）与低表达者活检后的生存率无差异。在21例接受CSF1R抑制剂治疗的患者中，基于CSF1R表达的无进展生存期或总生存期（从治疗开始）中位数也无显著差异（所有P值≥0.08）。在所有CSF1R表达≥第50百分位数的肿瘤样本中均观察到≥2种其他免疫检查点标志物（如PD-L1、BTLA、CTLA4、LAG3、TIM3）的同时上调。在进一步的大型前瞻性研究之前，CSF1R肿瘤高表达的患者可能需要联合靶向激活的特定免疫检查点途径的治疗，以影响预后。
