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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027055 | PMC |
http://dx.doi.org/10.1038/s41423-021-00634-7 | DOI Listing |
Front Immunol
January 2025
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
Introduction: Tuberculosis (TB) is the deadliest infectious disease worldwide and novel vaccines are urgently needed. HLA-E is a virtually monomorphic antigen presentation molecule and is not downregulated upon HIV co-infection. HLA-E restricted specific CD8 T cells are present in the circulation of individuals with active TB (aTB) and infection (TBI) with or without HIV co-infection, making HLA-E restricted T cells interesting vaccination targets for TB.
View Article and Find Full Text PDFHLA
January 2025
Kirov Hematology and Blood Transfusion Research Institute Under the Federal Medicine and Biology Agency, Federal State Budget Research Institution, Kirov, Russia.
Six novel HLA class I alleles were detected during the HLA typing process.
View Article and Find Full Text PDFCell Biol Toxicol
January 2025
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Background: Microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC) patients are the dominant population in immune checkpoint blockade treatments, while more than half of them could not benefit from single-agent immunotherapy. We tried to identify the biomarker of MSI-H CRC and explore its role and mechanism in anti-PD-1 treatments. Tumor-specific MHC-II was linked to a better response to anti-PD-1 in MSI-H CRC and CD74 promoted assembly and transport of HLA-DR dimers.
View Article and Find Full Text PDFAnaplastic lymphoma kinase (ALK)-fusion proteins resulting from chromosomal rearrangements are promising targets for cancer immunotherapy. While ALK-specific CD8+ T cells and epitopes presented on MHC class I have been identified in patients with ALK-positive malignancies, little is known about ALK-specific CD4+ T cells. We screened peripheral blood of ten ALK-positive anaplastic large cell lymphoma (ALK+ALCL) patients in remission and six healthy donors for CD4+ T-cell responses to the whole ALK-fusion protein, nucleophosmin (NPM1)::ALK.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Medical Biology and Genetics, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
Antigen presentation plays a critical role in the pathogenesis of immune-mediated disorders. This study aimed to investigate the effects of IFN-γ and a cytokine mix (5MIX: IL-1α, IL-17A, IL-22, OsM, and TNF-α) on the antigen-presenting capabilities of keratinocytes, with a specific focus on immune-mediated dermatological conditions such as psoriasis (Ps). To achieve this, keratinocytes were treated with IFN-γ and 5MIX, and their impact on the expression of key antigen-presentation molecules, HLA-DRα and CD74, was assessed.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!