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Review Open Access

Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review)

  • Authors:
    • Min Liu
    • Kui Su
  • View Affiliations / Copyright

    Affiliations: Department of Oral Medicine, School of Stomatology, Jinan University, Guangzhou, Guangdong 510632, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 139
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    Published online on: March 19, 2026
       https://doi.org/10.3892/etm.2026.13135
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Abstract

The excessive buildup of lactic acid within the tumor microenvironment (TME) serves as a hallmark of metabolic reprogramming in cancer. New studies have revealed that lactic acid is an energy metabolic product and a core biological signal that regulates the malignant process of tumors. It plays multiple roles in metabolic reprogramming, protein lactate modification, immune escape, drug resistance generation, epigenetic regulation and metastatic spread. It also has significant negative implications for patient survival. In this review, the advances in understanding the metabolic mechanisms of lactate in the TME and its crosstalk with various of immune cells were systematically reviewed and its therapeutic potential in the following ways was explored: Targeting lactate synthesis (e.g., lactate dehydrogenase inhibitors); interfering with lactate catabolism (e.g., monocarboxylate transporter blockers); and regulating lactate shuttling (microenvironmental cell‑to‑cell communication). The review aimed to identify new targets and ideas for anticancer strategies by analyzing the lactate metabolic network.
View Figures

Figure 1

Warburg effect and the reverse
Warburg effect. MCT, monocarboxylate transporter; GLUT, glucose
transporter.

Figure 2

Role of lactic acid in the TME. TME,
tumor microenvironment; TCA, tricarboxylic acid; KG,
ketoglutarate.

Figure 3

Crosstalk between lactic acid and
various immune cells. TAM, tumor-associated macrophage; T cell, T
lymphocyte; Treg, regulatory T cell; NK cell, natural killer cell;
CAF, cancer-associated fibroblast; DC, dendritic cell; ERK,
extracellular signal-regulated kinase; STAT, signal transducer and
activator of transcription; GRP, G protein-coupled receptor; CAMP,
cyclic adenosine monophosphate; ICER, inducible cAMP early
repressor; ARG, arginase; VEGF, vascular endothelial growth factor;
NFAT, nuclear factor of activated T cells; PD-1, programmed cell
death protein 1; mTOR, mechanistic target of rapamycin; NKP46,
natural cytotoxicity triggering receptor 1; NKG2D, natural killer
group 2, member D; p38, p38 mitogen-activated protein kinase; JNK,
c-Jun N-terminal kinase; c-Jun, Cellular Jun (proto-oncogene),
component of AP-1 transcription factor; HIF, hypoxia-inducible
factor.

Figure 4

Process of lactic acid
production.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Liu M and Su K: Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review). Exp Ther Med 31: 139, 2026.
APA
Liu, M., & Su, K. (2026). Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review). Experimental and Therapeutic Medicine, 31, 139. https://doi.org/10.3892/etm.2026.13135
MLA
Liu, M., Su, K."Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review)". Experimental and Therapeutic Medicine 31.5 (2026): 139.
Chicago
Liu, M., Su, K."Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review)". Experimental and Therapeutic Medicine 31, no. 5 (2026): 139. https://doi.org/10.3892/etm.2026.13135
Copy and paste a formatted citation
x
Spandidos Publications style
Liu M and Su K: Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review). Exp Ther Med 31: 139, 2026.
APA
Liu, M., & Su, K. (2026). Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review). Experimental and Therapeutic Medicine, 31, 139. https://doi.org/10.3892/etm.2026.13135
MLA
Liu, M., Su, K."Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review)". Experimental and Therapeutic Medicine 31.5 (2026): 139.
Chicago
Liu, M., Su, K."Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review)". Experimental and Therapeutic Medicine 31, no. 5 (2026): 139. https://doi.org/10.3892/etm.2026.13135
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