Lactylation Antibodies: How to Decode the Dialogue Mechanism Between Tumor Metabolism and Immunity?

I. What is the Molecular Nature of Histone Lactylation?

Histone lactylation is an emerging epigenetic modification mechanism whose molecular basis involves the covalent binding of a lactate group via an amide bond to specific lysine residues on the N-terminal tails of histones. Identified modification sites include H3K18, H3K27, H4K5, and H4K8, among others. This modification process is mediated by specific catalytic enzymes; notably, acetyltransferases like p300/CBP have been found to also possess lactyltransferase activity, capable of transferring metabolically produced lactate molecules to specific histone sites.

Functionally, histone lactylation plays a significant role in gene expression regulation. This modification typically enriches in gene promoter and enhancer regions, promoting the transcriptional activation of specific genes by altering chromatin spatial conformation. Research indicates that the gene regulatory networks involving lactylation primarily relate to key biological processes such as immunosuppressive pathways, cell survival and migration, extracellular matrix remodeling, and resistance to cell death.

II. What are the Technical Advantages of Lactylation Antibodies?

Lactylation-specific antibodies are crucial tools for studying this modification, mainly comprising two categories: pan-lactylation antibodies and site-specific antibodies. Pan-lactylation antibodies can detect global changes in lactylation levels, providing an overall modification context for research. In contrast, site-specific antibodies (e.g., H3K18la antibody) can precisely locate dynamic changes at specific modification sites, offering accurate information for mechanistic analysis.

Technically, lactylation antibodies are compatible with various experimental methods. Western blotting allows semi-quantitative analysis of lactylation levels; immunofluorescence and immunohistochemistry enable visualization of the spatial distribution of lactylation within cells and tissues; and chromatin immunoprecipitation followed by sequencing can reveal the genomic localization of lactylation modifications and their association with gene expression. The integrated application of these techniques provides powerful support for a deeper understanding of the biological functions of lactylation.

III. How Does Lactylation Drive Tumor Immune Escape?

In the tumor microenvironment, lactylation promotes immune escape through multiple mechanisms. Studies in glioblastoma show that elevated lactate levels in cancer stem cells enhance histone lactylation, which subsequently upregulates the expression of the immune checkpoint molecule CD47 via the CBX3-EP300 complex. CD47, acting as a "don't eat me" signal, inhibits macrophage phagocytosis of tumor cells, thereby facilitating immune escape.

Experimental evidence indicates that sodium lactate treatment significantly reduces the phagocytosis rate of tumor cells by macrophages, while the lactate dehydrogenase inhibitor DCA can reverse this effect. In animal models, combination therapy with DCA and anti-CD47 antibodies demonstrated synergistic anti-tumor effects, significantly inhibiting tumor growth and prolonging survival. These findings reveal the potential value of combining metabolic intervention with immunotherapy.

IV. How Does Lactylation Mediate Therapy Resistance?

In studies on metastasis after microwave ablation in liver cancer, lactylation was found to play a key role in promoting ferroptosis resistance. Sublethal heat stress induces enhanced glycolysis and lactate accumulation, leading to increased H3K18 lactylation levels. This modification specifically enriches at the NFS1 gene locus, promoting its transcriptional upregulation.

NFS1, a key factor in iron-sulfur cluster assembly, has its increased expression enhancing cellular resistance to ferroptosis, thereby promoting the metastatic potential of tumor cells. Functional experiments confirmed that knocking down NFS1 expression significantly increased tumor cell sensitivity to oxaliplatin, and combined intervention effectively suppressed the metastatic process in animal models. This mechanism provides new insights into understanding recurrence after local therapy.

V. What are the Key Strategies for Lactylation Research?

For lactylation research, a multi-level integrated strategy is recommended. At the metabolic level, analyze glycolytic capacity using Seahorse analysis combined with metabolomics to quantify lactate levels. At the epigenetic level, utilize lactylation antibodies to detect modification changes, combined with CUT&Tag technology to locate genomic enrichment regions. At the functional level, design specific intervention experiments to validate phenotype associations.

In mechanistic studies, focus on hub regulatory factors, including transcription factors, reader proteins, and modifying enzymes. Use techniques like site-directed mutagenesis, interaction analysis, and subcellular localization to decipher the functions of these factors within the lactylation network. Simultaneously, consider employing reversible intervention strategies, such as combining metabolic inhibitors with epigenetic drugs, to validate the targetability of the mechanism.

VI. What is the Clinical Significance of Lactylation Research?

Lactylation research holds significant clinical translational value. In diagnostics, lactylation levels may serve as biomarkers for prognosis assessment. Studies show that H3K18 lactylation levels correlate with poor prognosis in various tumors, and its detection can aid in patient risk stratification. In therapeutics, intervention strategies targeting the lactylation pathway offer new directions for combination therapy.

Based on existing evidence, strategies combining metabolic intervention with immune checkpoint inhibitors, or lactylation modulation with chemotherapy, show promising prospects. Future research should focus on integrating basic discoveries with clinical needs, validating the clinical value of lactylation through multi-center cohorts, and promoting the development of related targeted drugs, ultimately achieving a complete translation from mechanism to clinic.

VII. Which Companies Supply Lactylation Antibodies?

Hangzhou Start Biotech Co., Ltd. has independently developed the "L-Lactyl Lysine Rabbit Polyclonal Antibody" (Product Name: L-Lactyl Lysine Rabbit Polyclonal Antibody, Product Code: S0B0719). This is an epigenetic research tool characterized by high modification specificity, broad recognition capability, and excellent affinity. Prepared using carefully designed synthetic peptide immunogens and rigorously validated across multiple platforms including Immunoprecipitation, Western Blot, and Immunofluorescence, it holds significant application value in emerging frontier areas such as metabolism-epigenetics crossover research, gene expression regulation, and disease mechanism exploration.

Core Product Advantages:

• High Modification Specificity and Broad Recognition Capability: Cross-validated with modified/unmodified peptides, this product accurately recognizes L-lactylation modifications occurring on lysine residues, while showing almost no cross-reactivity with other common acylations (e.g., acetylation, crotonylation). Its polyclonal nature enables it to recognize lactylation modifications across different protein backgrounds, offering wide coverage.
• Excellent Affinity and Batch-to-Batch Stability: The product exhibits high affinity, effectively enriching and detecting endogenous lactylated proteins. Through strict serum pool management and purification processes, high consistency in performance across different product batches is ensured, providing reliable support for long-term research projects.

Suitable for Various Key Application Scenarios: This product is an ideal tool for the following research areas:

• Metabolite Sensing and Signal Transduction Research: For exploring how lactate acts as a signaling molecule to regulate cell function by inducing protein lactylation, linking cellular metabolism with epigenetic states.
• Immune and Inflammatory Response Regulation: For studying the role of lactylation in immunometabolic reprogramming during processes like macrophage polarization and in the tumor microenvironment.
• Gene Expression and Chromatin Regulation: For identifying lactylation sites on histones and investigating their novel functions in transcriptional activation and chromatin dynamics.
• Disease Mechanism and Biomarker Discovery: For exploring aberrant protein lactylation and its pathophysiological significance in tumors, metabolic diseases, and infectious diseases.

Professional Technical Support: We provide detailed product technical documentation, including specificity validation data, experimental protocols for various application platforms, a recommended target list, and professional technical consultation, fully committed to assisting customers in achieving leading discoveries in the rapidly evolving field of metabolic epigenetics.

Hangzhou Start Biotech Co., Ltd. is consistently dedicated to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more details about the "L-Lactyl Lysine Rabbit Polyclonal Antibody" (Product Code S0B0719) or to request a sample test, please feel free to contact us.

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