Yamashita Kohei, Iwatsuki Masaaki, Ajani Jaffer A, Baba Hideo
Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.
Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer Center Houston TX USA.
Ann Gastroenterol Surg. 2020 Jun 11;4(4):369-378. doi: 10.1002/ags3.12348. eCollection 2020 Jul.
Cancer immunotherapy has caused a paradigm shift from conventional therapies that directly target cancer cells to innovative therapies that utilize the host immune system. In particular, programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors have achieved an impressive breakthrough and been approved for clinical use in several types of cancer including gastrointestinal (GI) cancer. To identify and develop predictive biomarkers for PD-1 inhibitors is of great concern in clinical practice. Although PD-L1 expression is considered a logical biomarker as PD-L1 is a substantial target of the immune checkpoint inhibitors, its clinical significance in GI cancer remains unclear. In this review, we summarize the current evidence for PD-L1 expression as a prognostic and predictive biomarker for PD-1/PD-L1 inhibitors in GI cancer from recent publications, and emerging evidence from recent key clinical trials on the efficacy of PD-1/PD-L1 inhibitors. Challenging clinical issues for PD-L1 assessment are then discussed from the viewpoint of the methodology for PD-L1 evaluation including the differences in PD-L1 detection assays and evaluation criteria for PD-L1 positivity. Moreover, we highlight the biological features of PD-L1 expression in terms of tumor spatial and temporal heterogeneity, which suggests important implications for biomarker analysis. Finally, we describe future perspectives using liquid biopsy for better assessment of PD-L1 status. This new information should improve our understanding of the clinical significance of PD-L1 in GI cancer, leading to optimal patient selection and treatment strategy for the clinical use of PD-1/PD-L1 inhibitors in patients with GI cancer.
癌症免疫疗法已引发了一场范式转变，从直接靶向癌细胞的传统疗法转向利用宿主免疫系统的创新疗法。特别是，程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）抑制剂已取得了令人瞩目的突破，并已获批用于包括胃肠道（GI）癌在内的多种癌症的临床治疗。在临床实践中，识别和开发PD-1抑制剂的预测生物标志物备受关注。尽管PD-L1表达被认为是一种合理的生物标志物，因为PD-L1是免疫检查点抑制剂的主要靶点，但其在胃肠道癌中的临床意义仍不明确。在本综述中，我们总结了近期出版物中关于PD-L1表达作为胃肠道癌中PD-1/PD-L1抑制剂的预后和预测生物标志物的现有证据，以及近期关于PD-1/PD-L1抑制剂疗效的关键临床试验的新证据。然后，从PD-L1评估方法的角度讨论了PD-L1评估面临的具有挑战性的临床问题，包括PD-L1检测方法的差异和PD-L1阳性的评估标准。此外，我们强调了PD-L1表达在肿瘤空间和时间异质性方面的生物学特征，这对生物标志物分析具有重要意义。最后，我们描述了使用液体活检更好地评估PD-L1状态的未来前景。这些新信息应能增进我们对PD-L1在胃肠道癌中的临床意义的理解，从而为胃肠道癌患者临床使用PD-1/PD-L1抑制剂提供最佳的患者选择和治疗策略。
