ArticleCell death & disease2026
Lactylation stabilizes PD-L1 to promote tumor immune evasion and cell growth.
Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- circZNF148 Drives Glucose Metabolism Reprogramming to Enhance Metastasis and Immune Evasion via HK1 Stabilization in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Michelolide Enhances the Anticancer Efficacy of Radiation by Downregulating PD-L1 Protein Levels in Tumor Cells.International journal of molecular sciences · 2026Article
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Review
- The microbiota-host metabolic axis in cervical cancer: from homeostatic disruption to mechanisms of therapy resistance.Frontiers in cellular and infection microbiology · 2026Review
- The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.Frontiers in immunology · 2026Review
- Mechanical stress, metabolic reprogramming and stromal remodeling: an emerging paradigm in the bladder cancer mechano-micro-environment.Frontiers in genetics · 2026Review
- Aminoacyl-tRNA synthetases in tumor immunity: canonical translation, source-resolved immune circuits and therapeutic opportunities.Frontiers in immunology · 2026Review
- Non-histone lactylation in cancer: current advances and clinical implications.Frontiers in immunology · 2026Review
- GUDCA drives colorectal cancer progression via ALKBH5-mediated m6A modification of ENO1 and glycolytic reprogramming.Frontiers in pharmacology · 2026Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Programmed death-ligand 1 (PD-L1) plays a critical role in tumor immune evasion, yet the mechanisms that regulate its expression, specifically the metabolic control of its stability and function, remain elusive. In this study, we demonstrate that lactate, a key metabolite in the tumor microenvironment, upregulates PD-L1 expression via lysine lactylation (Kla) of PD-L1 at residue K280 within its intracellular domain. This modification stabilizes PD-L1 by inhibiting E3 ligase HUWE1 binding, ubiquitination, and subsequent proteasomal degradation. We identified alanyl-tRNA synthetase 1 (AARS1) as the lactyltransferase that utilizes lactate as a lactyl-donor and is responsible for PD-L1 K280 lactylation. Functionally, PD-L1 lactylation promotes tumor immune evasion by impairing CD8 + T cell-mediated cytotoxicity and accelerates tumor growth in vivo. Furthermore, sodium lactate (NaLa) administration enhances the efficacy of anti-PD-L1 immunotherapy in preclinical models. Clinically, PD-L1 K280 lactylation correlates with advanced non-small cell lung cancer stages and poor patient survival, highlighting its potential as a diagnostic biomarker. Our findings unveil a novel lactate-PD-L1 regulatory axis and propose lactylation as a therapeutic target to augment the efficacy of the immune checkpoint blockade.
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