ArticleJournal for immunotherapy of cancer2022
Tumorous expression of NAC1 restrains antitumor immunity through the LDHA-mediated immune evasion.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- AI-guided discovery of the IRF4-PAICS-LDHA axis as a multitarget hub linking tumor metabolism to CD8+ T cell exhaustion in DLBCL.NPJ precision oncology · 2026Article
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- Integrative machine learning models reveal immune and metabolic signatures predictive of colorectal cancer prognosis.Discover oncology · 2026Article
- Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance.Gastroenterology report · 2026Review
- Immunometabolic reprogramming in osteoporosis-osteoarthritis comorbidity: from inflammaging to osteochondral unit degeneration.Frontiers in immunology · 2026Review
- The role of the transcription factor PATZ1 in tumorigenesis and metabolic regulation.Journal of cancer research and clinical oncology · 2025Review
- Transforming acidic coiled-coil-containing protein 3-mediated lipid metabolism reprogramming impairs CD8Signal transduction and targeted therapy · 2025Article
- Metabolic fitness of NAC1-deficient Tregs in the tumor microenvironment fuels tumor growth.JCI insight · 2025Article
- Harnessing glycolysis in gastric cancer: molecular targets, therapeutic strategies, and clinical horizons.Frontiers in immunology · 2025Review
- Glycolysis-Driven Immune Evasion in Microsatellite Instability-High Colorectal Cancer: An Integrated Single-Cell and Spatial Transcriptomics Study.OncoTargets and therapy · 2025Article
- Nucleus Accumbens Associated Protein 1 in Cancers-The Real Value.International journal of molecular sciences · 2024Article
- Article
- NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development.Oncogenesis · 2024Article
- IL-6-Driven Autocrine Lactate Promotes Immune Escape of Uveal Melanoma.Investigative ophthalmology & visual science · 2024Article
- Exploring the regulatory mechanism of intestinal flora based on PD-1 receptor/ligand targeted cancer immunotherapy.Frontiers in immunology · 2024Review
- Case report: A novelFrontiers in psychiatry · 2024Article
- Control of CD4Signal transduction and targeted therapy · 2023Article
- Co-Targeting Nucleus Accumbens Associate 1 and NF-κB Signaling Synergistically Inhibits Melanoma Growth.Biomedicines · 2023Article
- Effects of altered glycolysis levels on CD8Cell death & disease · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundT cell-mediated antitumor immunity has a vital role in cancer prevention and treatment; however, the immune-suppressive tumor microenvironment (TME) constitutes a significant contributor to immune evasion that weakens antitumor immunity. Here, we explore the relationship between nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the BTB (broad-complex, Tramtrack, bric a brac)/POZ (Poxvirus, and Zinc finger) gene family, and the TME.
methodsAdoptive cell transfer (ACT) of mouse or human tumor antigen (Ag)-specific CD8
resultsTumorous expression of NAC1 negatively impacts the CTL-mediated antitumor immunity via lactate dehydrogenase A (LDHA)-mediated suppressive TME. NAC1 positively regulated the expression of LDHA at the transcriptional level, which led to higher accumulation of lactic acid in the TME. This inhibited the cytokine production and induced exhaustion and apoptosis of CTLs, impairing their cell-killing ability. In the immunocompetent and immunodeficient mice, NAC1 depleted melanoma tumors grew significantly slower and had an elevated infiltration of tumor Ag-specific CTLs following ACT, compared with the control groups.
conclusionsTumor expression of NAC1 contributes substantially to immune evasion through its regulatory role in LDHA expression and lactic acid production. Thus, therapeutic targeting of NAC1 warrants further exploration as a potential strategy to reinforce cancer immunotherapy, such as the ACT of CTLs.
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Registered trials
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