High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors
High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors
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DOI：
10.1186/s40425-018-0479-7
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发表时间：
2018-12-27
影响因子：
10.9
通讯作者：
Vareki, Saman Maleki
中科院分区：
文献类型：
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作者：
Vareki, Saman Maleki
对免疫检查点抑制剂（ICI）有反应的肿瘤具有较高水平的免疫浸润和/或指示T细胞发炎表型的干扰素（IFN）特征。黑色素瘤和肺癌表现出对ICI的高反应率，通常被称为热肿瘤。这些与具有低免疫浸润的肿瘤形成鲜明对比，称为冷肿瘤或非T细胞发炎的癌症，例如来自前列腺和胰腺的癌症。基于免疫表型的肿瘤分类可以部分解释对ICI的临床反应。然而，单凭这一模型并不能完全解释许多接受ICI治疗的患者缺乏反应，根据突变谱将肿瘤分为高肿瘤突变负荷（TMB）或低TMB，如许多儿童恶性肿瘤，也可以在一定程度上解释免疫治疗的临床反应。该模型主要关注肿瘤的基因型，而不是其免疫表型。高TMB肿瘤通常具有更高水平的可被免疫系统识别的新抗原。在当前的免疫治疗时代，由于缺乏明确的生物标志物，我们需要根据肿瘤的免疫表型和基因组突变谱来评估肿瘤，以确定哪些患者对ICI治疗有更高的反应可能性。
Tumors responding to immune checkpoint inhibitors (ICIs) have a higher level of immune infiltrates and/or an Interferon (IFN) signature indicative of a T-cell-inflamed phenotype. Melanoma and lung cancer demonstrate high response rates to ICIs and are commonly referred to as hot tumors. These are in sharp contrast to tumors with low immune infiltrates called cold tumors or non-T-cell-inflamed cancers, such as those from the prostate and pancreas. Classification of tumors based on their immune phenotype can partially explain clinical response to ICIs. However, this model alone cannot fully explain the lack of response among many patients treated with ICIs.Dichotomizing tumors based on their mutation profile into high tumor mutation burden (TMB) or low TMB, such as many childhood malignancies, can also, to some extent, explain the clinical response to immunotherapy. This model mainly focuses on a tumor's genotype rather than its immune phenotype. High TMB tumors often have higher levels of neoantigens that can be recognized by the immune system. In the current era of immunotherapy, with the lack of definitive biomarkers, we need to evaluate tumors based on both their immune phenotype and genomic mutation profile to determine which patients have a higher likelihood of responding to treatment with ICIs.