HLA class I loss in colorectal cancer: implications for immune escape and immunotherapy
Open accessAbstract
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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Loss of functional MHC class I molecules on tumour cells due to genetic or epigenetic alterations or transcriptional downregulation occurs in 30-40% of MSS tumours and precludes antigen-dependent tumour cell killing by CD8+ T cells.
“For example, loss of functional MHC class I (MHC-I) molecules on tumour cells due to genetic or epigenetic alterations or transcriptional downregulation occurs in 30–40% of MSS tumours and precludes antigen-dependent tumour cell killing by CD8+ T cells.167”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [167]
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Research works printed but not linked: 1
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Current and emerging concepts for systemic treatment of metastatic colorectal cancer
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- Authors
- Anderson, P., Aptsiauri, N., Ruiz-Cabello, F., & Garrido, F.
- Affiliations
- Instituto de Investigación Biosanitaria de Granada (ES)
- Universidad de Granada (ES)
- Corresponding author
- Garrido, Federico
- Venue
- Cellular & Molecular Immunology
- Published
- 2021-01-20
- Volume
- 18
- Issue
- 3
- Pages
- 556-565
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC8027055
- OpenAlex
- W3122102740
- Cited by
- 107
- References
- 145
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 23 · 2023: 23 · 2022: 18 · 2021: 9
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- HLA class I loss, colorectal cancer, tumor immune evasion, HLA class II, tumor antigens, T cell therapy, predictive biomarkers, molecular subtypes, metastasis, tumor heterogeneity, immune cell infiltration
- MeSH terms
- Animals, Humans, Immunotherapy, T-Lymphocytes, Cytotoxic, Colorectal Neoplasms, Histocompatibility Antigens Class I, Tumor Escape
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