Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples from the patients in the trial were collected and evaluated to discover potential biomarkers. The obtained samples were assessed for immunohistochemistry, ELISA and RNA sequencing. Their correlations with clinical outcome were analyzed. A high albumin level was significantly associated with improved progression-free survival (PFS), overall survival (OS) and disease control. Non-liver metastatic disease showed prolonged PFS and OS. Low regulatory T-cell (Treg) infiltration correlated with prolonged PFS. Low MIP-1β was associated with durable response and improved OS significantly. Upregulation of 23 genes, including CAPN9, NAPSA and ROS1, was observed in the durable disease control group, and upregulation of 10 genes, including MRPS18A, MAIP1 and CMTR2, was associated with a statistically significant improvement of PFS. This study suggests that pretreatment albumin, MIP-1β, non-liver metastatic disease and Treg infiltration may be potential predictive biomarkers of regorafenib/nivolumab in pMMR colorectal cancer. Further studies are needed to confirm these findings.
此前，我们在I/Ib期研究中报道了瑞戈非尼/纳武利尤单抗在错配修复功能完整（pMMR）型难治性结直肠癌中具有适度但持久的抗癌活性。这一发现提示需要生物标志物来更好地筛选患者。我们收集并评估了该试验患者的基线临床病理特征、血液及肿瘤样本，以探索潜在的生物标志物。对获取的样本进行了免疫组化、ELISA和RNA测序分析，并评估其与临床结局的相关性。结果显示，高水平白蛋白与改善的无进展生存期（PFS）、总生存期（OS）及疾病控制率显著相关；非肝转移性疾病患者的PFS和OS更长；低调节性T细胞（Treg）浸润与PFS延长相关；低MIP-1β水平与持久应答及OS显著改善相关。在持久疾病控制组中观察到包括CAPN9、NAPSA和ROS1在内的23个基因表达上调，而MRPS18A、MAIP1和CMTR2等10个基因的上调与PFS的统计学显著改善相关。本研究表明，治疗前白蛋白水平、MIP-1β、非肝转移状态及Treg浸润可能作为pMMR结直肠癌患者接受瑞戈非尼/纳武利尤单抗治疗的潜在预测性生物标志物，但尚需进一步研究验证。
肿瘤(癌症)患者之家