创作:Lexi 审核:Lexi 2019年11月18日
  • 不同的突变负担只能部分解释微卫星不稳性(MSI)和微卫星稳定(MSS)的结直肠癌(CRCs)对免疫治疗的不同反应;
  • 使用现有的预测算法测量肿瘤抗原负载并不能为临床治疗方案的设计提供足够精确的参考和指导;
  • 肿瘤组织中丰富的免疫细胞浸润可能具有较高的预后价值,但其并不能有效预测患者对免疫治疗的反应;
  • MSI和MSS结直肠癌细胞的内在特征决定了它们在进化上的差异,并影响免疫系统对肿瘤克隆和亚克隆动力学的塑造方式。
使用免疫检查点抑制剂进行免疫治疗是一种被批准的治疗方法,适用于表现出微卫星不稳定性的部分结直肠癌(CRC)患者。然而在这个患者亚群中,并不是所有个体都对免疫治疗有反应,并且有效的患者分层生物标志物仍然较为缺乏。最新发表在Trends in Cancer的观点文章,提供了不同的生物学参数的概述,有助于定义对免疫治疗敏感的微卫星不稳性CRC。该观点文章认为肿瘤与免疫细胞之间相互作用的动态特性使传统生物标志物的开发复杂化,并认为借鉴进化遗传学的新一代适应性指标可能提高临床决策的有效性和可靠性。
Trends in Cancer [IF:8.884]

Immunogenomics of Colorectal Tumors: Facts and Hypotheses on an Evolving Saga



2019-11-06, Review

Abstract & Authors:展开

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.

First Authors:
Irene Catalano,Elena Grassi

Correspondence Authors:
Livio Trusolino

All Authors:
Irene Catalano,Elena Grassi,Andrea Bertotti,Livio Trusolino