BACKGROUND The clinical success of immune checkpoint inhibitors demonstrates that reactivation of the human immune system delivers durable responses for some patients and represents an exciting approach for cancer treatment. An important class of preclinical in vivo models for immuno-oncology is immunocompetent mice bearing mouse syngeneic tumors. To facilitate translation of preclinical studies into human, we characterized the genomic, transcriptomic, and protein expression of a panel of ten commonly used mouse tumor cell lines grown in vitro culture as well as in vivo tumors. RESULTS Our studies identified a number of genetic and cellular phenotypic differences that distinguish commonly used mouse syngeneic models in our study from human cancers. Only a fraction of the somatic single nucleotide variants (SNVs) in these common mouse cell lines directly match SNVs in human actionable cancer genes. Some models derived from epithelial tumors have a more mesenchymal phenotype with relatively low T-lymphocyte infiltration compared to the corresponding human cancers. CT26, a colon tumor model, had the highest immunogenicity and was the model most responsive to CTLA4 inhibitor treatment, by contrast to the relatively low immunogenicity and response rate to checkpoint inhibitor therapies in human colon cancers. CONCLUSIONS The relative immunogenicity of these ten syngeneic tumors does not resemble typical human tumors derived from the same tissue of origin. By characterizing the mouse syngeneic models and comparing with their human tumor counterparts, this study contributes to a framework that may help investigators select the model most relevant to study a particular immune-oncology mechanism, and may rationalize some of the challenges associated with translating preclinical findings to clinical studies.

中文翻译：

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普通小鼠同基因模型与人类肿瘤的分子和细胞表型的比较。

背景技术免疫检查点抑制剂的临床成功表明，人类免疫系统的重新激活为某些患者提供了持久的应答，并代表了一种令人兴奋的癌症治疗方法。免疫肿瘤学的一类重要的临床前体内模型是带有小鼠同源肿瘤的具有免疫能力的小鼠。为了促进临床前研究向人类的翻译，我们对一组十种常用的体外培养以及体内肿瘤生长的常用小鼠肿瘤细胞系的基因组，转录组和蛋白质表达进行了表征。结果我们的研究确定了许多遗传和细胞表型差异，这些差异将我们研究中常用的小鼠同基因模型与人类癌症区分开来。在这些常见的小鼠细胞系中，只有一小部分的体细胞单核苷酸变体（SNV）与人类可操作的癌症基因中的SNV直接匹配。与相应的人类癌症相比，某些源自上皮肿瘤的模型具有更间充质表型，且T淋巴细胞浸润相对较低。结肠癌模型CT26具有最高的免疫原性，并且是对CTLA4抑制剂治疗反应最强的模型，与之相比，人类结肠癌的免疫原性和对检查点抑制剂疗法的应答率相对较低。结论这十种同基因肿瘤的相对免疫原性与源自同一起源组织的典型人类肿瘤不同。通过表征小鼠同源基因模型并与人类肿瘤对应模型进行比较，