A lactate molecule leaves a sugar-burning cancer cell like a road-weary saxophonist stepping off a late train: not exactly glamorous, carrying too much baggage, but somehow about to change the whole room.
For years, lactate had a lousy reputation. In gym lore, it got blamed for “the burn.” In cancer biology, it was treated like exhaust from the tumor engine: cancer cells gobble glucose, crank through glycolysis, and dump lactate into the neighborhood. Case closed. Somebody sweep up after the metabolic jam session.
But the new review by Fang and colleagues in Signal Transduction and Targeted Therapy argues that lactate is not just metabolic trash. It may be a signal, a fuel, an immune negotiator, and, through a process called lactylation, an epigenetic bandleader telling genes when to come in for the solo (DOI: 10.1038/s41392-026-02672-x).
The Tumor Neighborhood Has Weird Acoustics
Tumors do not grow in empty space. They live in the tumor microenvironment, which is basically a sketchy neighborhood full of blood vessels, immune cells, fibroblasts, low oxygen, acidic pockets, and cancer cells behaving like they own the lease.
One classic feature of many tumors is the Warburg effect: cancer cells often favor glycolysis and lactate production even when oxygen is available. That sounds inefficient, like choosing a scooter for a cross-country tour, but it helps fast-growing cells make building blocks and adapt to stress.
The twist is that lactate does not just sit there. It can move between cells through monocarboxylate transporters, especially MCT1 and MCT4. Some cells export it. Others import it. One cell’s exhaust becomes another cell’s snack. Cancer biology, as usual, refuses to be normal for five consecutive minutes.
Lactylation: When Metabolism Grabs the Sheet Music
The truly cool key change came in 2019, when researchers showed that lactate can contribute to histone lactylation, a chemical mark on histone proteins that helps regulate gene activity (DOI: 10.1038/s41586-019-1678-1; PMCID: PMC6818755).
Histones are the spools DNA wraps around. Add chemical marks to them, and you can make nearby genes easier or harder to read. If DNA is the songbook, histone marks are sticky notes from a very opinionated music director: “Trumpets louder here. T-cells maybe sit this one out.”
Lactylation seems to link metabolism to gene expression. High lactate can influence chromatin accessibility, immune behavior, DNA repair, cell plasticity, and therapy resistance. Fang and colleagues also highlight non-histone lactylation, meaning lactate-related marks may modify proteins beyond chromatin. That widens the stage considerably.
Immune Cells Are Trying to Play Through the Noise
The immune system is supposed to notice tumor cells and deal with them, like a security team with tiny molecular earpieces. But tumors are very good at messing with reception.
Lactate-rich, acidic tumor zones can suppress immune attack, reshape macrophages, and interfere with T-cell function. Reviews in tumor immunology now treat lactate as an active player in immune regulation, not just a leftover from sugar metabolism (DOI: 10.1016/j.it.2022.10.005; PMCID: PMC10905416).
But, because biology likes syncopation, lactate is not always the villain. One Nature Communications study found lactate could support stem-like CD8+ T cells and improve anti-tumor immunity in experimental systems (DOI: 10.1038/s41467-022-32521-8). So the question is not “Is lactate bad?” The question is: which cell, which tumor, which timing, which concentration, and which molecular dance floor?
Annoying? Yes. Scientifically useful? Also yes.
Turning Down the Lactate Amp
Therapeutically, the review points to several possible targets. Scientists are exploring ways to block lactate production through LDH inhibitors, stop lactate transport through MCT inhibitors, or interfere with enzymes that write, read, or erase lactylation marks.
The dream is not necessarily a solo drug that strolls onstage and saves the gig. More likely, lactate-targeted strategies could become harmonies: paired with chemotherapy, targeted therapy, radiation, or immunotherapy. If tumors use lactate to adapt, hide, repair damage, and resist treatment, then disrupting that system might make existing therapies hit cleaner notes.
That is the promise. The challenge is precision.
Lactate also matters in normal tissues. Your body uses it during exercise, wound healing, immune responses, and everyday metabolism. Blocking lactate biology with the subtlety of a cymbal crash could cause collateral problems. Researchers still need better biomarkers to identify lactate-dependent tumors, better maps of lactylation in human samples, and better ways to tell helpful immune effects from tumor-protective ones.
The Riff Worth Remembering
Fang and colleagues are asking us to retire the old idea that lactate is merely cancer’s metabolic garbage. In some tumors, lactate may be a strategy: a way to remodel the neighborhood, tune gene expression, influence immune cells, and help malignant cells survive bad weather.
If these findings keep holding up across tumor types and patient samples, the impact could be big. Oncologists may eventually profile tumors not only by mutations, but by metabolic wiring and epigenetic marks like lactylation. Treatment plans could start sounding less like a single melody and more like a smart jazz chart: block the fuel line, retune the immune response, hit the DNA repair trick, and bring the therapy back in on beat.
Cancer cells have been improvising for a long time. The useful move now is to learn the changes well enough to interrupt the solo.
References
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Fang C, Zhou S, Yu K, et al. Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances. Signal Transduction and Targeted Therapy. 2026;11:190. https://doi.org/10.1038/s41392-026-02672-x
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Zhang D, Tang Z, Huang H, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574:575-580. https://doi.org/10.1038/s41586-019-1678-1. PMCID: PMC6818755
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Apostolova P, Pearce EL. Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment. Trends in Immunology. 2022;43:969-977. https://doi.org/10.1016/j.it.2022.10.005. PMCID: PMC10905416
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Feng Q, Liu Z, Yu X, et al. Lactate increases stemness of CD8+ T cells to augment anti-tumor immunity. Nature Communications. 2022;13:4981. https://doi.org/10.1038/s41467-022-32521-8
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Dey P, Kimmelman AC, DePinho RA. Metabolic codependencies in the tumor microenvironment. Cancer Discovery. 2021;11:1067-1081. https://doi.org/10.1158/2159-8290.CD-20-1211
Disclaimer: The image accompanying this article is for illustrative purposes only and does not depict actual experimental results, data, or biological mechanisms.