期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 18, 期 3, 页码 556-565出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-021-00634-7
关键词
Colorectal cancer; Immune escape; HLA Class I
类别
资金
- Instituto de Salud Carlos III
- European Regional Development Fund (FEDER) [PI11/01386, PI14/01978, PI16/00752, PI17/00197, PI18/00826]
- Consejeria de Salud, Junta de Andalucia through the contract 'Nicolas Monardes' [C-0013-2018]
T cell-mediated immune therapies show promise in treating various malignancies, but only a small fraction of patients respond to treatment. Understanding the lack of responses and identifying predictive biomarkers is crucial. CRC is a heterogeneous disease, and the loss of HLA-I in CRC is associated with immune evasion and metastasis.
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.
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