美国哈佛医学院Stephen J. Elledge研究组发现，适应性免疫系统是选择肿瘤抑制基因 (TSG)失活的主要驱动力。2021年9月17日出版的《科学》杂志发表了这项成果。

他们在同基因小鼠肿瘤模型中进行了体内 CRISPR 筛选，以检查在有和没有适应性免疫选择压力的情况下对肿瘤发生的要求。在测试的每种肿瘤类型中，他们发现相对于免疫功能低的小鼠，在适应性免疫系统存在的情况下，TSG的丢失显著增加。近三分之一的 TSG 显示出优先富集，通常以癌症和组织特异性方式。

这些结果表明，在癌症中发现的复发性突变的克隆选择主要是由肿瘤逃逸适应性免疫系统的需要驱动的。

研究人员表示，在肿瘤发生过程中，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做到这一点。

附：英文原文

Title: The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation

Author: Timothy D. Martin, Rupesh S. Patel, Danielle R. Cook, Mei Yuk Choi, Ajinkya Patil, Anthony C. Liang, Mamie Z. Li, Kevin M. Haigis, Stephen J. Elledge

Issue&Volume: 2021-09-17

Abstract: 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.

DOI: abg5784

Source: https://www.science.org/doi/10.1126/science.abg5784