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Abstract：
Next generation immunotherapies have limited efficacy in colorectal cancer. Immune checkpoints inhibitors demonstrated their benefit in mismatch repair-deficient tumors, which also exhibit microsatellite instability (MSI). The Consensual Molecular Subtype (CMS) classification has been recently proposed and highlights specific immune escape mechanisms for each subtype. CMS1 \"immune\" subtype is hypermutated with a favorable immune microenvironment for immune checkpoints inhibitors activity. Importantly, CMS1 is not restricted to MSI tumors and includes also exonucleasic domain POLE mutated tumors which are good candidates for immunotherapy. The scope of this comprehensive review is to described immune anomalies and propose immunomodulating strategies for each CMS subtype in colorectal cancer. Finally, the potential interest of tumor mutation burden and the Immunoscore® in colorectal cancer is discussed taking into account the molecular classification and obstacles to antitumoral immune activity.
摘要：
下一代免疫疗法在结直肠癌中的功效有限。免疫检查点抑制剂证明了它们在错配修复缺陷肿瘤中的益处，这也表现出微卫星不稳定性（MSI）。最近提出了合意分子亚型（CMS）分类，并强调了每种亚型的特定免疫逃逸机制。CMS1“免疫”亚型发生超突变，具有良好的免疫微环境，可用于免疫检查点抑制剂的活性。重要的是,CMS1不限于MSI肿瘤,并且还包括外核结构域POLE突变的肿瘤,其是用于免疫疗法的良好候选者。这篇综合综述的范围是描述免疫异常，并提出针对结直肠癌中每种CMS亚型的免疫调节策略。最后,考虑到分子分类和抗肿瘤免疫活性的障碍，讨论了肿瘤突变负担和Immunoscore®在结直肠癌中的潜在兴趣。
