ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non-Small Cell Lung Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis.Molecular diagnosis & therapy · 2023Pooled it
- Article
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- A lung squamous cell carcinoma demonstrating spontaneous partial regression of the primary tumor with lymph node metastasis: a case report with analysis of the tumor immune microenvironment.Translational lung cancer research · 2026Article
- Integrative analysis of T cell subset-specific ICOS expression and tumor HLA class I/II expression in lung adenocarcinoma: implications for their interaction and clinical outcome.Cancer immunology, immunotherapy : CII · 2026Article
- TNF-⍺-mediated myeloid-instructed CD14Cell reports. Medicine · 2026Article
- Lung cancer vaccines to enhance immune checkpoint inhibitor therapy: evidence and future perspectives.Journal of hematology & oncology · 2026Review
- Characterisation of tumor-infiltrating gamma-delta T cells in human colorectal cancer with MHC-I loss.Clinical & translational immunology · 2026Article
- Lineage plasticity and immune invisibility in primary SCLC and LUAD-to-SCLC transformation: antigen presentation loss and therapeutic redirection.Frontiers in immunology · 2026Review
- A novel multivariate framework for functional gene networks enrichment analysis.Frontiers in genetics · 2026Article
- IL-4 mediated TAP2 downregulation is a dominant and reversible mechanism of immune evasion and immunotherapy resistance in non-small cell lung cancer.Molecular cancer · 2025Article
- Multidimensional bioinformatics perspective on smoking-linked driver genes and immune regulatory mechanisms in non-small cell lung cancer.Journal of translational medicine · 2025Article
- Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.The Journal of experimental medicine · 2025Article
- The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.Frontiers in immunology · 2025Review
- Harnessing the immunomodulatory properties of HLA-G for advanced immunotherapies.Frontiers in immunology · 2025Review
- Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer.Frontiers in pharmacology · 2025Article
- A Novel Lysosome-Related Gene Signature Predicts Lung Cancer Prognosis: A Bioinformatics-Driven Study.Health science reports · 2024Article
- Spatial colocalization and combined survival benefit of natural killer and CD8 T cells despite profound MHC class I loss in non-small cell lung cancer.Journal for immunotherapy of cancer · 2024Article
- Pharmacological induction of MHC-I expression in tumor cells revitalizes T cell antitumor immunity.JCI insight · 2024Article
- The role of mesenchymal stem cells in cancer and prospects for their use in cancer therapeutics.MedComm · 2024Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
purposeTo analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non-small cell lung cancer (NSCLC). EXPERIMENTAL
designUsing spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell-specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II β chain in >700 immunotherapy-naïve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts.
resultsCancer cell-specific downregulation of HLA markers was identified in 30.4% of cases. β2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of β2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in <5% of lung malignancies. Tumors with cancer cell-specific β2M downregulation displayed reduced T cells and increased natural killer (NK)-cell infiltration. Samples with cancer cell HLA-A downregulation displayed modest increase in CD8
conclusionsOur results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naïve NSCLCs associated with distinct tumor microenvironment composition and patient survival.
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