Immunotherapy represents a groundbreaking approach for treating colorectal cancer (CRC), harnessing the body’s own immune system to target tumour cells more precisely than conventional chemotherapy. Immune checkpoint inhibitors, such as antibodies against PD-1, PD-L1, or CTLA-4, have shown remarkable efficacy in certain patients, leading to durable responses and improved survival. However, the majority of CRC cases have limited benefit from a single agent checkpoint blockade. There is a growing need to identify biomarkers that will improve the selection of patients who will best respond to therapy, as well as new targets to sensitise cancers to an immune checkpoint blockade. Unfortunately, the search for reliable biomarkers has been limited by our incomplete understanding of how immunotherapies modify the already complex immune response to cancer. Revolutionary techniques, such as genome-wide CRISPR/Cas9 screening combined with the appropriate validation systems such as in vivo mouse models and/or 3D organoid co-culture systems, are being used to address this knowledge gap. This review will focus on the use of immunotherapies in CRC, discuss why most CRC patients do not respond, and highlight in vitro, in vivo, and novel techniques for discovery of new targets for combination treatment.
免疫疗法代表了一种治疗结直肠癌（CRC）的突破性方法，它利用人体自身的免疫系统，比传统化疗更精确地靶向肿瘤细胞。免疫检查点抑制剂，如针对PD-1、PD-L1或CTLA-4的抗体，已在部分患者中显示出显著疗效，带来持久应答并改善生存期。然而，大多数结直肠癌病例从单一检查点阻断疗法中获益有限。当前亟需识别能够优化治疗患者选择的生物标志物，并寻找新的靶点以提高癌症对免疫检查点阻断的敏感性。遗憾的是，由于对免疫疗法如何改变已复杂的癌症免疫反应理解尚不全面，可靠生物标志物的探索受到限制。为填补这一知识空白，研究者正采用革命性技术，如全基因组CRISPR/Cas9筛选结合适当的验证系统（包括体内小鼠模型和/或3D类器官共培养系统）。本综述将聚焦免疫疗法在结直肠癌中的应用，探讨多数患者无应答的原因，并重点介绍用于发现联合治疗新靶点的体外、体内及新型技术。
Developing New Immunotherapy Approaches for Colorectal Cancer
肿瘤(癌症)患者之家