Introduction: Personalizing neoadjuvant therapy for locally advanced rectal cancer (LARC) requires identifying biomarkers that predict treatment response. This study aims to evaluate soluble immune checkpoints (sICPs) as predictive markers for neoadjuvant treatment response in LARC patients located in the middle and lower rectum. Materials and Methods: This prospective study included patients diagnosed with clinical stage T3 or T4 rectal cancer (RC) based on pelvic magnetic resonance imaging, with or without pelvic lymph node involvement. The modified Ryan scoring system was used to assess the response to neoadjuvant chemoradiotherapy (nCRT). Blood samples were collected from all RC patients before initiating nCRT. Various sICPs (sCD25, 4-1BB, B7.2, free active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, galectin-9), along with age, gender, stage, blood cell counts, and biochemical variables, were recorded and compared based on tumor regression grade (TRG). Results: Among 38 participants, lymphocyte count was higher, and platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet count were lower in patients with complete/near-complete response (TRG 0/1). In addition, TRG 0/1 patients had significantly lower levels of soluble galectin-9 than TRG 2/3 patients. Furthermore, platelet count was the only parameter that showed a significant difference among the three groups (TRG 0/1, TRG 2, and TRG 3). PLR demonstrated the highest sensitivity and specificity, with >80% for both measures. Conclusions: Lymphocyte count, PLR, NLR, platelet count, and galectin-9 may help predict favorable neoadjuvant treatment response in LARC patients, although without providing a definitive outcome. Personalized therapy based on these markers could enhance treatment decision making in LARC management.

中文翻译：

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使用可溶性免疫检查点预测局部晚期直肠癌新辅助放化疗的反应。

简介：局部晚期直肠癌 (LARC) 的个体化新辅助治疗需要识别预测治疗反应的生物标志物。本研究旨在评估可溶性免疫检查点（sICP）作为位于中下直肠的 LARC 患者新辅助治疗反应的预测标志物。材料和方法：这项前瞻性研究纳入了根据盆腔磁共振成像诊断为临床分期 T3 或 T4 直肠癌 (RC) 的患者，无论是否有盆腔淋巴结受累。改良的 Ryan 评分系统用于评估新辅助放化疗 (nCRT) 的反应。在开始 nCRT 之前，从所有 RC 患者采集血样。各种 sICP（sCD25、4-1BB、B7.2、游离活性 TGF-β1、CTLA-4、PD-L1、PD-1、Tim-3、LAG-3、galectin-9）以及年龄、性别、根据肿瘤消退等级（TRG）记录和比较分期、血细胞计数和生化变量。结果：在 38 名参与者中，完全/接近完全缓解（TRG 0/ 1）。此外，TRG 0/1患者的可溶性半乳糖凝集素9水平显着低于TRG 2/3患者。此外，血小板计数是三组（TRG 0/1、TRG 2 和 TRG 3）之间显示显着差异的唯一参数。PLR 表现出最高的敏感性和特异性，两项指标的敏感性和特异性均 >80%。结论：淋巴细胞计数、PLR、NLR、血小板计数和半乳糖凝集素 9 可能有助于预测 LARC 患者良好的新辅助治疗反应，尽管不能提供明确的结果。基于这些标志物的个性化治疗可以增强 LARC 管理中的治疗决策。