Immunotherapy with immune checkpoint inhibitors is an approved treatment option for a subpopulation of patients with colorectal cancers that display microsatellite instability. However, not all individuals within this subgroup respond to immunotherapy, and molecular biomarkers for effective patient stratification are still lacking. In this opinion article, we provide an overview of the different biological parameters that contribute to rendering colorectal cancers with microsatellite instability potentially sensitive to immunotherapy. We critically discuss the reasons why such parameters have limited predictive value and the implications therein. We also consider that a more informed knowledge of response determinants in this tumor subtype could help understand the mechanisms of immunotherapy resistance in microsatellite stable tumors. We conclude that the dynamic nature of the interactions between cancer and immune cells complicates conventional biomarker development and argue that a new generation of adaptive metrics, borrowed from evolutionary genetics, may improve the effectiveness and reliability of clinical decision making.

免疫检查点抑制剂的免疫疗法是显示微卫星不稳定的结直肠癌患者亚群的一种公认的治疗选择。然而，并非该亚组中的所有个体都对免疫疗法有反应，并且仍然缺乏有效的患者分层的分子生物标志物。在这篇观点文章中，我们提供了不同的生物学参数的概述，这些生物学参数有助于使具有微卫星不稳定性的结直肠癌对免疫疗法具有潜在的敏感性。我们批判性地讨论了为什么这些参数具有有限的预测价值的原因及其含义。我们还认为，在这种肿瘤亚型中对反应决定簇有更全面的了解可能有助于了解微卫星稳定肿瘤中免疫治疗耐药性的机制。