ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021
Aldehyde Dehydrogenase 2 Mediates Alcohol-Induced Colorectal Cancer Immune Escape through Stabilizing PD-L1 Expression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 64 citations in OpenAlex.
- Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.Genes & diseases · 2027Review
- Macrophage ALDH2 drives immunotherapy resistance by silencing CXCL9 through metabolic-epigenetic crosstalk.Nature communications · 2026Article
- ALDH2 inhibits FASN stabilization via the E3 ligase CBL to suppress lipid accumulation and liver cancer development.Biology direct · 2026Article
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- Immune-evasive stem cells: engineering tolerance and reprogramming microenvironments for regenerative therapy.Stem cell research & therapy · 2026Review
- Reduced YTHDF2 inhibits PD-L1 expression by stabilizing mCell death & disease · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Alcohol induces sorafenib resistance in hepatocellular carcinoma: A translational study.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Ambivalent Copper: Mechanistically Distinct Immune Effects Driving Innovation in Cancer Nanomedicine.Pharmaceutics · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Causal association between mitochondrial genes and colorectal cancer: a multi-omics Mendelian randomization study.Discover oncology · 2025Article
- Adipocyte CLDN5 promotes thermogenesis and energy expenditure through regulation of IL10 expression.Nature communications · 2025Article
- ID3 enhances PD-L1 expression by restructuring MYC to promote colorectal cancer immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CpG-Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2-Mediated Remodeling of Tumor-Associated Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Olink Profiling of Intestinal Tissue Identifies Novel Biomarkers For Colorectal Cancer.Journal of proteome research · 2025Article
- Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy.Cancer innovation · 2025Article
- An interpretable machine learning model using multimodal pretreatment features predicts pathological complete response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.Frontiers in immunology · 2025Article
- Potential Mechanisms and Effects of Dai Bai Jie Ethanol Extract in Preventing Acute Alcoholic Liver Injury.Current issues in molecular biology · 2024Article
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the great success of immunotherapy in a small subset of cancer patients, most colorectal cancer (CRC) patients do not respond to programmed cell death receptor 1 (PD-1) blockade immunotherapy. There is an urgent medical need to elucidate how cancer cells evade immune response and to develop novel means to boost the efficacy of immune checkpoint inhibitors. In this study, alcohol induces ligand programmed cell death receptor 1 (PD-L1) expression of CRC cells in vitro and in vivo. Alcohol exposure is shown to induce aldehyde dehydrogenase 2 (ALDH2) expression that is a crucial enzyme involved in alcohol metabolism, and low level of lymphocytes infiltration in the murine CRC model and patients. Intriguingly, ALDH2 and PD-L1 protein expression are positively correlated in tumor tissues from the CRC patients. Mechanistically, ALDH2 stabilizes PD-L1 protein expression by physically interacting with the intracellular segment of PD-L1 and inhibiting its proteasome-dependent degradation mediated by an E3 ubiquitin ligase Speckle Type POZ Protein (SPOP). Importantly, inhibition of ALDH2 reduces PD-L1 protein in CRC cells and promotes tumor-infiltrating T cells (TILs) infiltration, presumably leading to the significant potentiation of anti-PD-1 antibody efficacy in a mouse CT26 CRC model. The findings highlight a crucial role played by ALDH2 to facilitate alcohol-mediated tumor escape from immunity surveillance and promote tumor progression.
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