Chuang Chien-Huai, Guo Jhe-Cyuan, Kato Ken, Hsu Chih-Hung
Department of Medical Oncology, National Taiwan University Cancer Center, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Esophagus. 2025 Apr;22(2):139-147. doi: 10.1007/s10388-024-01105-4. Epub 2025 Jan 23.
Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly lethal malignancy in Asia. Recent advancements in immune checkpoint inhibitors (ICIs) have markedly transformed the systemic therapy landscape for ESCC. Anti-PD-1-based combination with chemotherapy or with ipilimumab, an anti-CTLA-4 antibody, have been established as the new standard first-line treatments for patients with advanced ESCC. Moreover, anti-PD-1 monotherapy has demonstrated improved efficacy and survival compared with second-line chemotherapy in previously treated patients with ESCC. Novel ICIs targeting other immune checkpoints also show potential for enhancing anticancer therapy in advanced ESCC.The TIGIT/PVR pathway represents a new immune checkpoint. Preclinical studies have indicated that the dual blockade of TIGIT and PD-1 can enhance antitumor immune responses. Clinical trials have reported that combining anti-TIGIT with anti-PD-1/PD-L1 antibodies elicited clinical responses in patients with advanced ESCC. In the first-line systemic therapy setting, combinations of dual ICIs targeting TIGIT and PD-1/PD-L1 plus platinum-based chemotherapy have demonstrated acceptable toxicity profiles and promising antitumor activity in several phase II trials and one phase III study. However, the role of adding an anti-TIGIT antibody to the current standard of anti-PD-1/PD-L1 plus platinum-based chemotherapy in first-line therapy for advanced ESCC remains to be fully determined, necessitating further clinical trials. Ongoing studies are also investigating the role of anti-TIGIT, with or without anti-PD-1/PD-L1, in locoregional ESCC. Additional research is essential to optimize the potential of anti-TIGIT therapy in ESCC and other malignancies by identifying predictive biomarkers, determining optimal antibody types, and gaining key mechanistic insights.
食管鳞状细胞癌（ESCC）在亚洲是一种常见且致死率很高的恶性肿瘤。免疫检查点抑制剂（ICI）的最新进展显著改变了ESCC的全身治疗格局。基于抗PD-1与化疗或与抗CTLA-4抗体伊匹木单抗联合使用，已被确立为晚期ESCC患者新的一线标准治疗方案。此外，在既往接受过治疗的ESCC患者中，抗PD-1单药治疗与二线化疗相比已显示出更高的疗效和更长的生存期。靶向其他免疫检查点的新型ICI在晚期ESCC的抗癌治疗中也显示出潜力。TIGIT/PVR通路代表一种新的免疫检查点。临床前研究表明，TIGIT和PD-1的双重阻断可增强抗肿瘤免疫反应。临床试验报告称，抗TIGIT与抗PD-1/PD-L1抗体联合使用可使晚期ESCC患者产生临床反应。在一线全身治疗中，靶向TIGIT和PD-1/PD-L1的双重ICI联合铂类化疗在多项II期试验和一项III期研究中已显示出可接受的毒性特征和有前景的抗肿瘤活性。然而，在晚期ESCC的一线治疗中，在当前抗PD-1/PD-L1加铂类化疗的标准方案中添加抗TIGIT抗体的作用仍有待充分确定，这需要进一步的临床试验。正在进行的研究也在调查抗TIGIT在局部区域性ESCC中的作用，无论是否联合抗PD-1/PD-L1。通过识别预测生物标志物、确定最佳抗体类型以及获得关键的机制性见解，开展更多研究对于优化抗TIGIT疗法在ESCC和其他恶性肿瘤中的潜力至关重要。
