Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States.
Department of Medical Oncology and Developmental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, United States.
World J Gastroenterol. 2018 Jul 7;24(25):2686-2697. doi: 10.3748/wjg.v24.i25.2686.
Blockade of the programmed death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction (GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability (MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatment-refractory solid tumors with MSI status and the third-line or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.
阻断程序性死亡配体 1（PD-L1）和程序性死亡受体 1（PD-1）受体轴代表了一种有效的癌症免疫治疗形式。临床前证据最初表明，胃和胃食管交界处（GEJ）癌症是潜在的免疫治疗敏感肿瘤。早期临床试验表明，PD-1/PD-L1 阻断在晚期或转移性胃/GEJ 癌中具有有前途的抗肿瘤活性。微卫星不稳定性（MSI）和 PD-L1 表达被证明可以预测对 PD-1 抑制剂更高的反应，这突出了 pembrolizumab 在 MSI 状态的治疗难治性实体瘤和 PD-L1 阳性晚期胃/GEJ 癌症的三线或以上治疗中的最近批准。然而，预测和预后生物标志物仍然是一个持续的需求。在这篇综述中，我们详细描述了临床前证据和早期组织生物标志物分析，说明了 PD-1/PD-L1 阻断在胃/GEJ 癌症中的潜在预测生物标志物。我们还回顾了 PD-1/PD-L1 抑制剂在胃/GEJ 癌症中的临床开发，并强调了未来需要进一步研究的几个领域，以优化 PD-1/PD-L1 阻断在胃/GEJ 癌症中的疗效。
