Gorría Teresa, Sierra-Boada Marina, Rojas Mariam, Figueras Carolina, Marin Silvia, Madurga Sergio, Cascante Marta, Maurel Joan
Medical Oncology Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain.
Translational Genomics and Targeted Therapies in Solid Tumors, Agustí Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.
Cancers (Basel). 2025 Feb 2;17(3):498. doi: 10.3390/cancers17030498.
Although immune checkpoint inhibitor (ICI) therapy is currently the standard of care in microsatellite-unstable (MSI) metastatic colorectal cancer (CRC), ICI therapy, alone or in combination with other therapies, is not a treatment approach in microsatellite-stable (MSS) CRC, which is present in 95% of patients. In this review, we focus on metabolic singularities-at the transcriptomic (either bulk or single cell), proteomic, and post-translational modification levels-that induce immunosuppression in cancer and specifically in MSS CRC. First, we evaluate the current efficacy of ICIs in limited and metastatic disease in MSS CRC. Second, we discuss the latest findings on the potential biomarkers for evaluating ICI efficacy in MSS CRC using strict REMARK criteria. Third, we review the current evidence on metabolic patterns in CRC tumors and immune cell metabolism to advance our understanding of metabolic crosstalk and to pave the way for the development of combination strategies to enhance ICI efficacy.
尽管免疫检查点抑制剂（ICI）疗法目前是微卫星不稳定（MSI）转移性结直肠癌（CRC）的标准治疗方法，但ICI疗法单独使用或与其他疗法联合使用，并非占95%患者的微卫星稳定（MSS）CRC的治疗方法。在本综述中，我们聚焦于代谢异常——在转录组（批量或单细胞）、蛋白质组和翻译后修饰水平上——这些异常在癌症尤其是MSS CRC中诱导免疫抑制。首先，我们评估ICI在MSS CRC的局限性和转移性疾病中的当前疗效。其次，我们使用严格的REMARK标准讨论关于评估MSS CRC中ICI疗效的潜在生物标志物的最新发现。第三，我们回顾CRC肿瘤和免疫细胞代谢中代谢模式的当前证据，以加深我们对代谢串扰的理解，并为开发增强ICI疗效的联合策略铺平道路。
