Weinberg Benjamin A, Hameed Rumaisa, Marshall John L
The Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
Inova Fairfax Hospital, Falls Church, Virginia.
Clin Adv Hematol Oncol. 2019 Feb;17(2):109-119.
Immunotherapy with checkpoint blockade of pro-grammed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has substantially increased the number of anticancer agents in our arsenal. However, these therapies are not effective in all cancer types, benefitting only a subset of patients with susceptible, immunogenic cancers. This problem is especially significant in gastrointestinal malignancies, which infrequently respond to immunotherapy. Although we clearly need more accurate biomarkers to predict response to immune checkpoint inhibition in gastrointestinal cancers, the established markers of mismatch repair deficiency, microsatellite instability, programmed death ligand 1 (PD-L1) expression, and tumor mutational burden are good starting points to identify patients who may benefit. Tumor-infiltrating lymphocytes, Epstein-Barr virus, and the stool microbiome are candidates for future immuno-oncology biomarkers in gastrointestinal malignancies. The availability of better biomarkers will improve patient selection for immunotherapy; it will also improve the design of clinical trials of agents intended for this population of patients, who require more effective treatment options.
对程序性死亡1（PD-1）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）进行检查点阻断的免疫疗法，极大地增加了我们抗癌药物的种类。然而，这些疗法并非对所有癌症类型都有效，仅使一部分患有易感性、免疫原性癌症的患者受益。这个问题在胃肠道恶性肿瘤中尤为突出，这类肿瘤对免疫疗法的反应很少见。虽然我们显然需要更准确的生物标志物来预测胃肠道癌症对免疫检查点抑制的反应，但错配修复缺陷、微卫星不稳定性、程序性死亡配体1（PD-L1）表达和肿瘤突变负荷等已确立的标志物，是识别可能受益患者的良好起点。肿瘤浸润淋巴细胞、爱泼斯坦-巴尔病毒和粪便微生物群，是胃肠道恶性肿瘤未来免疫肿瘤学生物标志物的候选对象。更好的生物标志物的出现，将改善免疫疗法的患者选择；它还将改善针对这类需要更有效治疗方案的患者群体的药物临床试验设计。
