Lactylation is rewriting Cancer Biology and Immunology

As a pioneer in lysine lactylation (Kla) antibodies, PTM BIO remains committed to advancing research within cancer biology and immunology. Notably, the study of lysine lactylation has rapidly gained momentum in these domains over the past few years, yielding a surge of innovative research findings.

Lactylation: The Metabolic Switch Rewriting Cellular Biology

For decades, lactate was viewed merely as a metabolic waste product of glycolysis. Today, it is recognized as a powerful epigenetic and post-translational modifier. With its lysine lactylation antibody portfolio, PTM BIO supports researchers investigating how this former byproduct is fundamentally reshaping our understanding of complex biological systems, particularly in the realms of oncology and immunology.

Cancer Biology: Driving Tumor Chemoresistance

In cancer biology, the focus of lactylation research has increasingly centered on how tumors hijack this mechanism to drive therapeutic resistance. For example, a tumor-derived lactate and ENO1 lactylation feedback loop has been shown to facilitate osimertinib resistance in lung adenocarcinoma. Similarly, in response to chemotherapy, the helicase BLM is highly lactylated, which improves its stability and promotes homologous recombination repair, ultimately leading to anthracycline resistance. Furthermore, targeting XLF lactylation, which ordinarily promotes non-homologous end-joining repair, has been shown to improve chemotherapy efficiency.

Interestingly, while early research focused heavily on histone lactylation, which primarily regulates gene transcription, there is a rapidly growing body of evidence highlighting the profound impact of non-histone protein lactylation. Non-histone lactylation triggers a much broader array of molecular mechanisms. It actively regulates signal transduction, modulates enzyme activity, and dictates protein stability. It also drives complex structural changes; for instance, lactylation of the m6A reader YTHDC1 regulates its phase separation, enhancing target mRNA stability to promote renal cell carcinoma progression. Additionally, it influences critical protein-protein interactions, such as enhancing XLF-Ku80 binding during DNA repair.

Notable research includes:

• Liu, B. et al. Targeting MYC in T-Cell lymphoma via epigenetic modulation with a small-molecule inhibitor. Molecular Cancer (2026).
• Gan, L. et al. A tumor-derived lactate/ENO1 lactylation feedback loop facilitates osimertinib resistance of lung adenocarcinoma. Drug Resistance Updates (2026).
• Shang, T. et al. The noncanonical function of liver-type phosphofructokinase potentiates the efficacy of HDAC inhibitors in cancer. Signal Transduction and Targeted Therapy (2025).
• Dai, C. et al. YTHDC1 lactylation regulates its phase separation to enhance target mRNA stability and promote RCC progression. Molecular Cell (2025).
• Jin, M. et al. Lactylation of XLF promotes non-homologous end-joining repair and chemoresistance in cancer. Molecular Cell (2025).
• Li, X. et al. Irinotecan alleviates chemoresistance to anthracyclines through the inhibition of AARS1-mediated BLM lactylation and homologous recombination repair. Signal Transduction and Targeted Therapy (2025).
• Zhu, J. et al. Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma. Cancer Communications (2025).

Immunology: Fine-Tuning Inflammation and Immune Memory

Lactylation also actively participates in dynamic antiviral defense. Viral infections trigger the lactylation of TBK1, which shapes antiviral immune responses by potentiating type I interferon signaling. Within the tumor microenvironment, high lactylation levels can compromise immune function; however, targeting and reducing these cellular lactylation levels successfully reinforces natural killer (NK) cell cytotoxicity, restoring their antileukemic activity.

Finally, lactylation leaves a lasting mark on innate immunity. Long-term histone lactylation (specifically H3K18la) connects metabolic and epigenetic rewiring in innate immune memory. This modification persists long after the initial training stimulus is eliminated, acting as a durable epigenetic mark that prepares the immune system for future challenges.

Key findings include:

• Zhao, Q. et al. Nonenzymatic lysine D-lactylation induced by glyoxalase II substrate SLG dampens inflammatory immune responses. Cell Research (2025).
• Xie, Y. et al. Dynamic regulation of TBK1 lactylation shapes antiviral immune responses. Cellular & Molecular Immunology (2026).
• Jin, J. et al. Targeting lactylation reinforces NK cell cytotoxicity within the tumor microenvironment. Nature Immunology (2025).
• Ziogas, A. et al. Long-term histone lactylation connects metabolic and epigenetic rewiring in innate immune memory. Cell (2025).

PTM BIO’s Lysine Lactylation Antibodies

PTM BIO provides a comprehensive suite of premium lysine lactylation antibodies. By delivering unparalleled precision, these tools empower researchers to navigate this rapidly evolving field, unlocking novel therapeutic avenues across oncology, neurodegeneration, and cardiovascular medicine. As the frontiers of lactylation research continue to expand, PTM BIO remains steadfast in its commitment to equipping scientists with the innovative solutions needed to fully decode its biological significance.

PTM BIO lysine lactylation antibodies are available through the Bio-Connect webshop. For product selection, application guidance or technical questions, please contact your account manager or our Technical support team.