During tumorigenesis, tumors must evolve to evade the immune system and do so by disrupting the genes involved in antigen processing and presentation or up-regulating inhibitory immune checkpoint genes. We performed in vivo CRISPR screens in syngeneic mouse tumor models to examine requirements for tumorigenesis both with and without adaptive immune selective pressure. In each tumor type tested, we found a marked enrichment for the loss of tumor suppressor genes (TSGs) in the presence of an adaptive immune system relative to immunocompromised mice. Nearly one-third of TSGs showed preferential enrichment, often in a cancer- and tissue-specific manner. These results suggest that clonal selection of recurrent mutations found in cancer is driven largely by the tumor’s requirement to avoid the adaptive immune system.

中文翻译：

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适应性免疫系统是选择肿瘤抑制基因失活的主要驱动力

在肿瘤发生期间，肿瘤必须进化以逃避免疫系统，并通过破坏参与抗原加工和呈递的基因或上调抑制性免疫检查点基因来逃避免疫系统。我们在同系小鼠肿瘤模型中进行了体内 CRISPR 筛选，以检查有无适应性免疫选择压力的肿瘤发生的要求。在每种测试的肿瘤类型中，我们发现相对于免疫功能低下的小鼠，在适应性免疫系统存在的情况下，肿瘤抑制基因 (TSGs) 的丢失显着富集。近三分之一的 TSG 表现出优先富集，通常以癌症和组织特异性方式进行。这些结果表明，在癌症中发现的复发突变的克隆选择主要是由肿瘤需要避免适应性免疫系统驱动的。