Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain.
Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, 18014, Granada, Spain.
Cell Mol Immunol. 2021 Mar;18(3):556-565. doi: 10.1038/s41423-021-00634-7. Epub 2021 Jan 20.
T cell-mediated immune therapies have emerged as a promising treatment modality in different malignancies including colorectal cancer (CRC). However, only a fraction of patients currently respond to treatment. Understanding the lack of responses and finding biomarkers with predictive value is of great importance. There is evidence that CRC is a heterogeneous disease and several classification systems have been proposed that are based on genomic instability, immune cell infiltration, stromal content and molecular subtypes of gene expression. Human leukocyte antigen class I (HLA-I) plays a pivotal role in presenting processed antigens to T lymphocytes, including tumour antigens. These molecules are frequently lost in different types of cancers, including CRC, resulting in tumour immune escape from cytotoxic T lymphocytes during the natural history of cancer development. The aim of this review is to (i) summarize the prevalence and molecular mechanisms behind HLA-I loss in CRC, (ii) discuss HLA-I expression/loss in the context of the newly identified CRC molecular subtypes, (iii) analyze the HLA-I phenotypes of CRC metastases disseminated via blood or the lymphatic system, (iv) discuss strategies to recover/circumvent HLA-I expression/loss and finally (v) review the role of HLA class II (HLA-II) in CRC prognosis.
T 细胞介导的免疫疗法已成为包括结直肠癌（CRC）在内的不同恶性肿瘤的一种有前途的治疗方法。然而，目前只有一部分患者对治疗有反应。了解缺乏反应的原因并找到具有预测价值的生物标志物非常重要。有证据表明 CRC 是一种异质性疾病，已经提出了几种分类系统，这些系统基于基因组不稳定性、免疫细胞浸润、基质含量和基因表达的分子亚型。人类白细胞抗原 I 类（HLA-I）在向包括肿瘤抗原在内的 T 淋巴细胞呈递加工抗原方面起着关键作用。这些分子在包括 CRC 在内的不同类型的癌症中经常丢失，导致肿瘤在癌症发展的自然史中逃避细胞毒性 T 淋巴细胞。本综述的目的是：（i）总结 CRC 中 HLA-I 丢失的流行率和分子机制，（ii）讨论新确定的 CRC 分子亚型背景下的 HLA-I 表达/丢失，（iii）分析通过血液或淋巴系统传播的 CRC 转移的 HLA-I 表型，（iv）讨论恢复/规避 HLA-I 表达/丢失的策略，最后（v）综述 HLA-II 在 CRC 预后中的作用。
