ArticleImmunogenetics2018
HLA class I alterations in breast carcinoma are associated with a high frequency of the loss of heterozygosity at chromosomes 6 and 15.
Article in Immunogenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 50 citations in OpenAlex.
- Hallmarks and correlates of effective adoptive cell immunotherapy for cancer.Nature reviews. Immunology · 2026Review
- Breast cancer immunotherapy: mechanisms of immune evasion, biomarkers, and emerging therapeutic strategies.Molecular cancer · 2026Review
- Immune Checkpoint Blockade and Emerging Combination Platforms in Breast Cancer: A Narrative Review.Breast cancer (Dove Medical Press) · 2026Review
- Neoadjuvant Immunotherapy in Hormone Receptor-Positive Breast Cancer: From Tumor Microenvironment Reprogramming to Combination Therapy Strategies.International journal of molecular sciences · 2025Review
- DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response.Cancer science · 2025Review
- Natural killer cells occupy unique spatial neighborhoods in HER2Breast cancer research : BCR · 2025Article
- Elevating MHC I expression on tumor cells by nanovesicles loading tyrosine kinase inhibitors can improve the efficacy of cancer vaccines.Frontiers in immunology · 2025Article
- Review
- Transcripts of repetitive DNA elements signal to block phagocytosis of hematopoietic stem cells.Science (New York, N.Y.) · 2024Article
- Detecting HLA loss of heterozygosity within a standard diagnostic sequencing workflow for prognostic and therapeutic opportunities.NPJ precision oncology · 2024Article
- The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer.Cancer medicine · 2024Review
- Germline homozygosity and allelic imbalance of HLA-I are common in esophagogastric adenocarcinoma and impair the repertoire of immunogenic peptides.Journal for immunotherapy of cancer · 2024Article
- Article
- Human Leukocyte Antigen Class I Expression and Natural Killer Cell Infiltration and Its Correlation with Prognostic Features in Luminal Breast Cancers.Breast cancer (Dove Medical Press) · 2024Article
- HER2 and HLA-A*02 dual CAR-T cells utilize LOH in a NOT logic gate to address on-target off-tumor toxicity.Journal for immunotherapy of cancer · 2023Article
- Inhibition of FGFR3 upregulates MHC-I and PD-L1 via TLR3/NF-kB pathway in muscle-invasive bladder cancer.Cancer medicine · 2023Article
- The evolving landscape of PCSK9 inhibition in cancer.European journal of pharmacology · 2023Review
- Emerging phagocytosis checkpoints in cancer immunotherapy.Signal transduction and targeted therapy · 2023Review
- Article
- Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.Nature cancer · 2023Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HLA class I (HLA-I) molecules play a crucial role in the presentation of tumor antigenic peptides to CD8+ T cells. Tumor HLA-I loss provides a route of immune escape from T cell-mediated killing. We analyzed HLA-I expression in 98 cryopreserved breast cancer tissues using a broad panel of anti-HLA-I antibodies. Genomic HLA-I typing was performed using DNA obtained from autologous normal breast tissue. Analysis of the loss of heterozygosity (LOH) in the HLA-I region of chromosome 6 (LOH-6) and in the β2-microglobulin (B2M) region of chromosome 15 (LOH-15) was done by microsatellite amplification of DNA isolated from microdissected tumor areas. B2M gene sequencing was done using this DNA form HLA-I-negative tumors. Immunohistological analysis revealed various types of HLA-I alterations in 79 tumors (81%), including total HLA-I loss in 53 cases (54%) and partial loss in 16 samples (14%). In 19 cases (19%), HLA-I expression was positive. Using microsatellite analysis, we detected LOH in 36 cases out of 92 evaluated (39%), including 15 samples with only LOH-6, 14 with LOH-15, and seven tumors with LOH-6 and LOH-15 at the same time. Remarkably, we detected LOH-6 in eight tumors with positive HLA-I immunolabeling. We did not find any B2M mutations in HLA-I-negative breast tumors. In conclusion, LOH at chromosomes 6 and 15 has a high incidence in breast cancer and occurs in tumors with different HLA-I immunophenotypes. This common molecular mechanism of HLA-I alterations may reduce the ability of cytotoxic T lymphocytes to kill tumor cells and negatively influence the clinical success of cancer immunotherapy.
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