免疫检查点抑制剂 (ICIs) 彻底改变了错配修复缺陷 (dMMR)/微卫星不稳定性高 (MSI-H) 胃肠道 (GI) 癌症的治疗。基于在转移环境中观察到的显着结果，多项临床试验研究了 ICI 作为局部 dMMR/MSI-H 胃肠道癌症的新辅助治疗 (NAT)，在临床和病理反应方面取得了惊人的结果，并为患者免于新辅助治疗创造了机会化疗和/或放疗，甚至手术切除。然而，这些令人印象深刻的发现主要来自小型概念验证第二阶段研究，仍然有几个悬而未决的问题需要解决。此外，dMMR/MSI-H 代表了一个有限的亚组，占胃肠道癌症的比例不到 10%。因此，考虑到免疫靶向药物与化疗和/或放疗等标准疗法相结合的潜在协同效应，人们做出了许多努力来研究错配修复熟练/微卫星稳定（MSS）癌症中的新辅助ICIs。然而，在未选择的人群中将 ICI 与护理标准相结合的结果仍然不能令人满意，在化疗中添加派姆单抗并没有改善食管胃腺癌的无事件生存率，并且有时对局部晚期直肠癌患者的获益有限。因此，一个主要的挑战将是在这种疾病的异质谱中识别出那些可以利用新辅助免疫疗法并提供最有效治疗的患者。在这篇综述中，我们讨论了 NAT 在胃肠道恶性肿瘤中的基本原理，总结了评估该治疗策略在 MSI-H 和 MSS 肿瘤中已完成的试验的现有证据。最后，我们讨论了正在进行的研究和未来的前景，以使新辅助免疫疗法成为治疗局部晚期胃肠道肿瘤的又一支箭。©作者（或其雇主）2024。CC BY-允许重复使用数控。禁止商业再利用。请参阅权利和权限。由英国医学杂志出版。

Immune checkpoint inhibitors (ICIs) revolutionized the management of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers. Based on notable results observed in the metastatic setting, several clinical trials investigated ICIs as neoadjuvant treatment (NAT) for localized dMMR/MSI-H GI cancers, achieving striking results in terms of clinical and pathological responses and creating the opportunity to spare patients from neoadjuvant chemotherapy and/or radiotherapy and even surgical resection. Nevertheless, these impressive findings are mainly derived from small proof of concept phase II studies and there are still several open questions to address. Moreover, dMMR/MSI-H represents a limited subgroup accounting for less than 10% of GI cancers. Consequently, many efforts have been produced to investigate neoadjuvant ICIs also in mismatch repair-proficient/microsatellite stable (MSS) cancers, considering the potential synergistic effect in combining immune-targeted agents with standard therapies such as chemo and/or radiotherapy. However, results for combining ICIs to the standard of care in the unselected population are still unsatisfactory, without improvements in event-free survival in esophago-gastric adenocarcinoma for the addition of pembrolizumab to chemotherapy, and sometimes limited benefit in patients with locally advanced rectal cancer. Therefore, a major challenge will be to identify among the heterogenous spectrum of this disease, those patients that could take advantage of neoadjuvant immunotherapy and deliver the most effective treatment. In this review we discuss the rationale of NAT in GI malignancies, summarize the available evidence regarding the completed trials that evaluated this treatment strategy in both MSI-H and MSS tumors. Finally, we discuss ongoing studies and future perspectives to render neoadjuvant immunotherapy another arrow in the quiver for the treatment of locally advanced GI tumors.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.