Department of Oncology, University of Western Ontario, London, ON, Canada.
Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada.
J Immunother Cancer. 2018 Dec 27;6(1):157. doi: 10.1186/s40425-018-0479-7.
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.
对免疫检查点抑制剂 (ICI) 有反应的肿瘤具有更高水平的免疫浸润和/或干扰素 (IFN) 特征，表明存在 T 细胞浸润表型。黑色素瘤和肺癌对 ICI 有很高的反应率，通常被称为“热肿瘤”。这些与免疫浸润水平较低的肿瘤形成鲜明对比，后者被称为“冷肿瘤”或非 T 细胞浸润性癌症，如前列腺癌和胰腺癌。根据肿瘤的免疫表型进行分类可以部分解释对 ICI 的临床反应。然而，仅这种模型无法完全解释许多接受 ICI 治疗的患者缺乏反应的情况。根据肿瘤的突变谱将肿瘤分为高肿瘤突变负担 (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。该模型主要侧重于肿瘤的基因型，而不是其免疫表型。高 TMB 肿瘤通常具有更高水平的新抗原，这些新抗原可以被免疫系统识别。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 治疗更有可能有反应。
