Cited by 107Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesGenetic factors in colorectal cancer

HLA class I loss in colorectal cancer: implications for immune escape and immunotherapy

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Anderson, Per, Aptsiauri, Natalia, Ruiz-Cabello, Francisco, Garrido, Federico·2021·Cellular & Molecular Immunology

Abstract

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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Crossref · 10.1038/s41423-021-00634-7

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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”

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Research works printed but not linked: 1

  1. [6]Mendez R, et al. Impact of HLA class I alterations in patients undergoing T cell specific immunotherapy. Immunobiology of the human MHC. Proc. 13th Int. Histocompatibility Workshop Conf. (IHWC) 2002. 2006;2:512–514. [Google Scholar]

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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
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
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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