Research progress on the regulation of tumor malignancy by lactate

Zhiling WANG; Wanjin CHEN; Shengtao CHENG

doi:10.19401/j.cnki.1007-3639.2025.11.009

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Research progress on the regulation of tumor malignancy by lactate

Review | 更新时间：2025-12-31

- Research progress on the regulation of tumor malignancy by lactate
- China Oncology Vol. 35, Issue 11, Pages: 1067-1075(2025)
- 作者机构：
  
  重庆医科大学感染性疾病分子生物学教育部重点实验室，重庆 400016
- 作者简介：
  
  CHENG Shengtao E-mail: shengtao@cqmu.edu.cn
- 基金信息：
  
  General Program of National Natural Science Foundation of China(82473089)
- DOI：10.19401/j.cnki.1007-3639.2025.11.009
  CLC： R730.2
- Received：14 April 2025，
  
  Revised：2025-07-15，
  
  Published：30 November 2025
- 稿件说明：
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Zhiling WANG, Wanjin CHEN, Shengtao CHENG. Research progress on the regulation of tumor malignancy by lactate[J]. China Oncology, 2025, 35(11): 1067-1075.
DOI：

Zhiling WANG, Wanjin CHEN, Shengtao CHENG. Research progress on the regulation of tumor malignancy by lactate[J]. China Oncology, 2025, 35(11): 1067-1075. DOI： 10.19401/j.cnki.1007-3639.2025.11.009.

摘要

恶性肿瘤作为全球公共卫生领域的重大挑战，迫切需要创新诊疗策略。乳酸作为肿瘤细胞糖酵解的重要代谢产物，不仅是能量代谢中间体，更以“代谢底物”和“信号分子”的双重身份参与肿瘤恶性进程的调控。具体而言，乳酸可通过单羧酸转运体（monocarboxylate transporter，MCT）介导的“乳酸穿梭”实现代谢物跨细胞分配，并借助组蛋白乳酰化修饰调控表观遗传，从而构建能量代谢、氨基酸代谢及脂代谢网络增强肿瘤细胞的代谢可塑性。在免疫调控层面，乳酸诱导T细胞向免疫抑制表型转化，阻碍CD8

T细胞记忆分化并削弱细胞毒性。同时，乳酸不仅能够降低自然杀伤（natural killer，NK）细胞的免疫效能，还通过诱导线粒体功能障碍触发凋亡，为转移灶创造免疫豁免生态位。此外，高水平乳酸激活多条信号转导通路，募集并诱导巨噬细胞向M2型转化，构建免疫逃逸微环境。治疗策略方面，当前研究围绕乳酸代谢的关键环节展开多维度探索。抑制乳酸合成已成为逆转肿瘤代谢优势的重要治疗策略，通过靶向调控乳酸生成和转运的关键分子，减少肿瘤微环境（tumor microenvironment，TME）中乳酸的蓄积，从而削弱其对代谢重编程的驱动作用。此外，促

进乳酸分解是当前极具潜力的代谢干预新方向，借助于生物酶或仿生催化系统，新型药物能够增强局部乳酸的清除效率，缓解酸性TME对免疫功能的抑制。本文系统综述乳酸介导的代谢-免疫调控网络，并探讨靶向乳酸通路的精准治疗策略，旨在打破肿瘤细胞的代谢适应性优势与免疫逃逸之间的恶性循环，为探索更高效的抗肿瘤疗法提供系统性的研究方向和转化思路。

Abstract

Malignant tumors represent a major global public health challenge

necessitating urgent innovation in diagnostic and therapeutic strategies. Lactate

a key metabolic product of tumor cell glycolysis

functions not merely as an energy metabolite but also as a signaling molecule to regulate malignant progression. Lactate mediates intercellular metabolite distribution through monocarboxylate transporter (MCT)-driven lactate shuttling and regulates epigenetics

via

histone lactylation. This integration establishes interconnected networks of energy

amino acid

and lipid metabolism that enhance tumor metabolic plasticity. In immune regulation

lactate induces a shift of T cells toward immunosuppressive phenotypes

impedes CD8

T cell memory differentiation

and attenuates cytotoxicity. Simultaneously

lactate not only reduces the immune efficacy of natural killer (NK) cells but also triggers apoptosis by inducing mitochondrial dysfunction

creating an immune-privileged niche for metastatic sites. Furthermore

elevated lactate levels activate multiple signaling pathways to recruit macrophages and drive their polarization toward the M2 phenotype

fostering an immunosuppressive microenvironment. Current therapeutic strategies target key aspects of lactate metabolism. Inhibiting lactate synthesis reduces lactate accumulation in tumor microenvironment (TME)

countering the tumor’s metabolic advantage and diminishing its role in driving metabolic reprogramming. Additionally

promoting the decomposition of lactate represents a promising new direction. Novel agents employing bioenzymes or biomimetic catalytic systems enhance local lactate clearance

alleviating the immunosuppressive effects of the acidic TME. This review comprehensively outlined the l

actate-mediated regulatory network

aiming to provide systematic research directions and translational insights for developing more effective anti-tumor therapies.

关键词

Keywords

references

CAO W , QIN K , LI F , et al . Socioeconomic inequalities in cancer incidence and mortality: an analysis of GLOBOCAN 2022 [J ] . Chin Med J (Engl) , 2024 , 137 ( 12 ): 1407 - 1413 .

郑荣寿 , 陈茹 , 韩冰峰 , 等 . 2022年中国恶性肿瘤流行情况分析 [J ] . 中华肿瘤杂志 , 2024 , 46 ( 3 ): 221 - 231 .

ZHENG R S , CHEN R , HAN B F , et al . Cancer incidence and mortality in China, 2022 [J ] . Chin J Oncol , 2024 , 46 ( 3 ): 221 - 231 .

BROOKS G A . The tortuous path of lactate shuttle discovery: from cinders and boards to the lab and ICU [J ] . J Sport Health Sci , 2020 , 9 ( 5 ): 446 - 460 . DOI: S2095-2546(20)30019-3 http://doi.org/S2095-2546(20)30019-3

WANG Q T , HU Y , WAN J L , et al . Lactate: a novel signaling molecule in synaptic plasticity and drug addiction [J ] . Bioessays , 2019 , 41 ( 8 ): e1900008 .

EMHOFF C W , MESSONNIER L A , HORNING M A , et al . Gluconeogenesis and hepatic glycogenolysis during exercise at the lactate threshold [J ] . J Appl Physiol ( 1985 ), 2013, 114 ( 3 ): 297 - 306 . DOI: 10.1152/japplphysiol.01202.2012 http://doi.org/10.1152/japplphysiol.01202.2012 https://www.physiology.org/doi/10.1152/japplphysiol.01202.2012 https://www.physiology.org/doi/10.1152/japplphysiol.01202.2012

SHAO C , TANG S , YU S Q , et al . Genetic code expansion reveals site-specific lactylation in living cells reshapes protein functions [J ] . Nat Commun , 2025 , 16 ( 1 ): 227 . DOI: 10.1038/s41467-024-55165-2 http://doi.org/10.1038/s41467-024-55165-2

HU Y , HE Z , LI Z , et al . Lactylation: the novel histone modification influence on gene expression, protein function, and disease [J ] . Clin Epigenetics , 2024 , 16 ( 1 ): 72 DOI: 10.1186/s13148-024-01682-2 http://doi.org/10.1186/s13148-024-01682-2

MAO Y , ZHANG J , ZHOU Q , et al . Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation [J ] . Cell Res , 2024 , 34 ( 1 ): 13 - 30 . DOI: 10.1038/s41422-023-00864-6 http://doi.org/10.1038/s41422-023-00864-6

LI L , CHEN K , WANG T , et al . Glis1 facilitates induction of pluripotency via an epigenome-metabolome-epigenome signalling cascade [J ] . Nat Metab , 2020 , 2 ( 9 ): 882 - 92 DOI: 10.1038/s42255-020-0267-9 http://doi.org/10.1038/s42255-020-0267-9

ZHAO Q H , WANG Q , YAO Q H , et al . Nonenzymatic lysine D-lactylation induced by glyoxalase Ⅱ substrate SLG dampens inflammatory immune responses [J ] . Cell Res , 2025 , 35 ( 2 ): 97 - 116 . DOI: 10.1038/s41422-024-01060-w http://doi.org/10.1038/s41422-024-01060-w

XU K , ZHANG K , WANG Y , et al . Comprehensive review of histone lactylation: structure, function, and therapeutic targets [J ] . Biochem Pharmacol , 2024 , 225 : 116331 . DOI: 10.1016/j.bcp.2024.116331 http://doi.org/10.1016/j.bcp.2024.116331 https://linkinghub.elsevier.com/retrieve/pii/S0006295224003149 https://linkinghub.elsevier.com/retrieve/pii/S0006295224003149

BROOKS G A . Cell-cell and intracellular lactate shuttles [J ] . J Physiol , 2009 , 587 ( Pt 23 ): 5591 - 5600 . DOI: 10.1113/tjp.2009.587.issue-23 http://doi.org/10.1113/tjp.2009.587.issue-23 https://physoc.onlinelibrary.wiley.com/toc/14697793/587/23 https://physoc.onlinelibrary.wiley.com/toc/14697793/587/23

FAUBERT B , LI K Y , CAI L , et al . Lactate metabolism in human lung tumors [J ] . Cell , 2017 , 171 ( 2 ): 358 - 371 .e9. DOI: S0092-8674(17)31068-1 http://doi.org/S0092-8674(17)31068-1

WANG W T , ZHOU Y , LI W , et al . Claudins and hepatocellular carcinoma [J ] . Biomed Pharmacother , 2024 , 171 : 116109 . DOI: 10.1016/j.biopha.2023.116109 http://doi.org/10.1016/j.biopha.2023.116109 https://linkinghub.elsevier.com/retrieve/pii/S0753332223019078 https://linkinghub.elsevier.com/retrieve/pii/S0753332223019078

WELCH D R . Tumor heterogeneity: a ‘contemporary concept’ founded on historical insights and predictions [J ] . Cancer Res , 2016 , 76 ( 1 ): 4 - 6 .

ENRÍQUEZ J A , MITTELBRUNN M . Warburg effect reshapes tumor immunogenicity [J ] . Cancer Res , 2024 , 84 ( 13 ): 2043 - 2045 . DOI: 10.1158/0008-5472.CAN-24-1304 http://doi.org/10.1158/0008-5472.CAN-24-1304

CAPATINA A L , MALCOLM J R , STENNING J , et al . Hypoxia-induced epigenetic regulation of breast cancer progression and the tumour microenvironment [J ] . Front Cell Dev Biol , 2024 , 12 : 1421629 . DOI: 10.3389/fcell.2024.1421629 http://doi.org/10.3389/fcell.2024.1421629 https://www.frontiersin.org/articles/10.3389/fcell.2024.1421629/full https://www.frontiersin.org/articles/10.3389/fcell.2024.1421629/full

ZHANG G Q , XI C , JU N T , et al . Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer [J ] . J Endocrinol Invest , 2024 , 47 ( 8 ): 1953 - 1969 . DOI: 10.1007/s40618-023-02294-y http://doi.org/10.1007/s40618-023-02294-y

XUAN D T M , WU C C , WANG W J , et al . Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway [J ] . Int J Med Sci , 2023 , 20 ( 1 ): 35 - 49 . DOI: 10.7150/ijms.75625 http://doi.org/10.7150/ijms.75625

MA Y , LING S K , LI Y , et al . Loss of heterozygosity for Kras G12D promotes malignant phenotype of pancreatic ductal adenocarcinoma by activating HIF-2α-c-myc-regulated glutamine metabolism [J ] . Int J Mol Sci , 2022 , 23 ( 12 ): 6697 . DOI: 10.3390/ijms23126697 http://doi.org/10.3390/ijms23126697 https://www.mdpi.com/1422-0067/23/12/6697 https://www.mdpi.com/1422-0067/23/12/6697

WEN Q , HUANG M H , XIE J W , et al . lncRNA SYTL5-OT4 promotes vessel co-option by inhibiting the autophagic degradation of ASCT2 [J ] . Drug Resist Updat , 2023 , 69 : 100975 . DOI: 10.1016/j.drup.2023.100975 http://doi.org/10.1016/j.drup.2023.100975 https://linkinghub.elsevier.com/retrieve/pii/S1368764623000584 https://linkinghub.elsevier.com/retrieve/pii/S1368764623000584

HU H X , TAKANO N , XIANG L S , et al . Hypoxia-inducible factors enhance glutamate signaling in cancer cells [J ] . Oncotarget , 2014 , 5 ( 19 ): 8853 - 8868 . DOI: 10.18632/oncotarget.2593 http://doi.org/10.18632/oncotarget.2593

LAU A , BLENIS J , BURGOS-BARRAGAN G . Decoding serine metabolism: unveiling novel pathways for evolving cancer therapies [J ] . Cancer Res , 2024 , 84 ( 8 ): 1191 - 1194 . DOI: 10.1158/0008-5472.CAN-24-0541 http://doi.org/10.1158/0008-5472.CAN-24-0541

LU Y X , ZHU J H , ZHANG Y X , et al . Lactylation-driven IGF2BP3-mediated serine metabolism reprogramming and RNA m6A-modification promotes lenvatinib resistance in HCC [J ] . Adv Sci (Weinh) , 2024 , 11 ( 46 ): e2401399 .

QIAO Z , LI Y , LI S M , et al . Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells [J ] . Mol Cell Biochem , 2024 , 479 ( 11 ): 3063 - 3076 . DOI: 10.1007/s11010-023-04913-x http://doi.org/10.1007/s11010-023-04913-x

NAGANA GOWDA G A , LUSK J A , PASCUA V . Intracellular pyruvate-lactate-alanine cycling detected using real-time nuclear magnetic resonance spectroscopy of live cells and isolated mitochondria [J ] . Magn Reson Chem , 2024 , 62 ( 2 ): 84 - 93 . DOI: 10.1002/mrc.v62.2 http://doi.org/10.1002/mrc.v62.2 https://analyticalsciencejournals.onlinelibrary.wiley.com/toc/1097458xa/62/2 https://analyticalsciencejournals.onlinelibrary.wiley.com/toc/1097458xa/62/2

GREEN C R , ALAEDDINE L M , WESSENDORF-RODRIGUEZ K A , et al . Impaired branched-chain amino acid (BCAA) catabolism during adipocyte differentiation decreases glycolytic flux [J ] . J Biol Chem , 2024 , 300 ( 12 ): 108004 . DOI: 10.1016/j.jbc.2024.108004 http://doi.org/10.1016/j.jbc.2024.108004 https://linkinghub.elsevier.com/retrieve/pii/S0021925824025067 https://linkinghub.elsevier.com/retrieve/pii/S0021925824025067

KONDO A , YAMAMOTO S , NAKAKI R , et al . Extracellular acidic pH activates the sterol regulatory element-binding protein 2 to promote tumor progression [J ] . Cell Rep , 2017 , 18 ( 9 ): 2228 - 2242 . DOI: S2211-1247(17)30171-7 http://doi.org/S2211-1247(17)30171-7

IPPOLITO L , COMITO G , PARRI M , et al . Lactate rewires lipid metabolism and sustains a metabolic-epigenetic axis in prostate cancer [J ] . Cancer Res , 2022 , 82 ( 7 ): 1267 - 1282 . DOI: 10.1158/0008-5472.CAN-21-0914 http://doi.org/10.1158/0008-5472.CAN-21-0914

CORBET C , BASTIEN E , SANTIAGO DE JESUS J P , et al . TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells [J ] . Nat Commun , 2020 , 11 ( 1 ): 454 . DOI: 10.1038/s41467-019-14262-3 http://doi.org/10.1038/s41467-019-14262-3

IPPOLITO L , COMITO G , PARRI M , et al . Lactate rewires lipid metabolism and sustains a metabolic-epigenetic axis in prostate cancer [J ] . Cancer Res , 2022 , 82 ( 7 ): 1267 - 82 . DOI: 10.1158/0008-5472.CAN-21-0914 http://doi.org/10.1158/0008-5472.CAN-21-0914

MENG Y , GUO D , LIN L , et al . Glycolytic enzyme PFKL governs lipolysis by promoting lipid droplet-mitochondria tethering to enhance β-oxidation and tumor cell proliferation [J ] . Nat Metab , 2024 , 6 ( 6 ): 1092 - 107 . DOI: 10.1038/s42255-024-01047-2 http://doi.org/10.1038/s42255-024-01047-2

WAN J , CHENG C , HU J J , et al . De novo NAD + synthesis contributes to CD8 + T cell metabolic fitness and antitumor function [J ] . Cell Rep , 2023 , 42 ( 12 ): 113518 . DOI: 10.1016/j.celrep.2023.113518 http://doi.org/10.1016/j.celrep.2023.113518 https://linkinghub.elsevier.com/retrieve/pii/S2211124723015309 https://linkinghub.elsevier.com/retrieve/pii/S2211124723015309

TURNER L , VAN LE T N , CROSS E , et al . Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics [J ] . Sci Immunol , 2024 , 9 ( 93 ): eadj7238.

PAN W L , TSOKOS M G , SCHERLINGER M , et al . The PP2A regulatory subunit PPP2R2A controls NAD + biosynthesis to regulate T cell subset differentiation in systemic autoimmunity [J ] . Cell Rep , 2024 , 43 ( 7 ): 114379 . DOI: 10.1016/j.celrep.2024.114379 http://doi.org/10.1016/j.celrep.2024.114379 https://linkinghub.elsevier.com/retrieve/pii/S2211124724007071 https://linkinghub.elsevier.com/retrieve/pii/S2211124724007071

CHEN X Y , LIU L L , KANG S W , et al . The lactate dehydrogenase (LDH) isoenzyme spectrum enables optimally controlling T cell glycolysis and differentiation [J ] . Sci Adv , 2023 , 9 ( 12 ): eadd9554.

PERALTA R M , XIE B X , LONTOS K , et al . Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism [J ] . Nat Immunol , 2024 , 25 ( 12 ): 2297 - 2307 . DOI: 10.1038/s41590-024-01999-3 http://doi.org/10.1038/s41590-024-01999-3

FANG Y , LIU W R , TANG Z , et al . Monocarboxylate transporter 4 inhibition potentiates hepatocellular carcinoma immunotherapy through enhancing T cell infiltration and immune attack [J ] . Hepatology , 2023 , 77 ( 1 ): 109 - 123 . DOI: 10.1002/hep.32348 http://doi.org/10.1002/hep.32348 https://journals.lww.com/10.1002/hep.32348 https://journals.lww.com/10.1002/hep.32348

BARBIERI L , VELIÇA P , GAMEIRO P A , et al . Lactate exposure shapes the metabolic and transcriptomic profile of CD8 + T cells [J ] . Front Immunol , 2023 , 14 : 1101433 . DOI: 10.3389/fimmu.2023.1101433 http://doi.org/10.3389/fimmu.2023.1101433 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1101433/full https://www.frontiersin.org/articles/10.3389/fimmu.2023.1101433/full

D’ARIA S , MAQUET C , LI S , et al . Expression of the monocarboxylate transporter MCT1 is required for virus-specific mouse CD8 + T cell memory development [J ] . Proc Natl Acad Sci USA , 2024 , 121 ( 13 ): e2306763121.

SUKUMAR M , LIU J , JI Y , et al . Inhibiting glycolytic metabolism enhances CD8 + T cell memory and antitumor function [J ] . J Clin Invest , 2013 , 123 ( 10 ): 4479 - 4488 . DOI: 10.1172/JCI69589 http://doi.org/10.1172/JCI69589 http://www.jci.org/articles/view/69589 http://www.jci.org/articles/view/69589

WATSON M J , VIGNALI P D A , MULLETT S J , et al . Metabolic support of tumour-infiltrating regulatory T cells by lactic acid [J ] . Nature , 2021 , 591 ( 7851 ): 645 - 651 . DOI: 10.1038/s41586-020-03045-2 http://doi.org/10.1038/s41586-020-03045-2

KONDO M , KUMAGAI S , NISHIKAWA H . Metabolic advantages of regulatory T cells dictated by cancer cells [J ] . Int Immunol , 2024 , 36 ( 2 ): 75 - 86 . DOI: 10.1093/intimm/dxad035 http://doi.org/10.1093/intimm/dxad035 https://academic.oup.com/intimm/article/36/2/75/7317563 https://academic.oup.com/intimm/article/36/2/75/7317563

ZHANG Y N , HUANG Y T , HONG Y , et al . Lactate acid promotes PD-1 + Tregs accumulation in the bone marrow with high tumor burden of acute myeloid leukemia [J ] . Int Immunopharmacol , 2024 , 130 : 111765 . DOI: 10.1016/j.intimp.2024.111765 http://doi.org/10.1016/j.intimp.2024.111765 https://linkinghub.elsevier.com/retrieve/pii/S1567576924002832 https://linkinghub.elsevier.com/retrieve/pii/S1567576924002832

TUOMELA K , LEVINGS M K . Acidity promotes the differentiation of immunosuppressive regulatory T cells [J ] . Eur J Immunol , 2023 , 53 ( 6 ): 2350511 . DOI: 10.1002/eji.v53.6 http://doi.org/10.1002/eji.v53.6 https://onlinelibrary.wiley.com/toc/15214141/53/6 https://onlinelibrary.wiley.com/toc/15214141/53/6

RAO D S , STUNNENBERG J A , LACROIX R , et al . Acidity-mediated induction of FoxP3 + regulatory T cells [J ] . Eur J Immunol , 2023 , 53 ( 6 ): e2250258 .

ZHANG Y T , XING M L , FANG H H , et al . Effects of lactate on metabolism and differentiation of CD4 + T cells [J ] . Mol Immunol , 2023 , 154 : 96 - 107 . DOI: 10.1016/j.molimm.2022.12.015 http://doi.org/10.1016/j.molimm.2022.12.015 https://linkinghub.elsevier.com/retrieve/pii/S0161589022005053 https://linkinghub.elsevier.com/retrieve/pii/S0161589022005053

ZHANG W H , YUAN S J , ZHANG Z P , et al . Regulating tumor cells to awaken T cell antitumor function and enhance melanoma immunotherapy [J ] . Biomaterials , 2025 , 316 : 123034 . DOI: 10.1016/j.biomaterials.2024.123034 http://doi.org/10.1016/j.biomaterials.2024.123034 https://linkinghub.elsevier.com/retrieve/pii/S0142961224005702 https://linkinghub.elsevier.com/retrieve/pii/S0142961224005702

MA J W , TANG L , TAN Y Y , et al . Lithium carbonate revitalizes tumor-reactive CD8 + T cells by shunting lactic acid into mitochondria [J ] . Nat Immunol , 2024 , 25 ( 3 ): 552 - 561 . DOI: 10.1038/s41590-023-01738-0 http://doi.org/10.1038/s41590-023-01738-0

GE W L , MENG L D , CAO S J , et al . The SIX1/LDHA axis promotes lactate accumulation and leads to NK cell dysfunction in pancreatic cancer [J ] . J Immunol Res , 2023 , 2023 : 6891636 .

BRAND A , SINGER K , KOEHL G E , et al . LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells [J ] . Cell Metab , 2016 , 24 ( 5 ): 657 - 671 . DOI: S1550-4131(16)30427-2 http://doi.org/S1550-4131(16)30427-2

LUO Z H , HUANG X H , XU X Y , et al . Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression [J ] . Cancer Biol Med , 2024 , 21 ( 6 ): 513 - 540 .

NETSKAR H , PFEFFERLE A , GOODRIDGE J P , et al . Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping [J ] . Nat Immunol , 2024 , 25 ( 8 ): 1445 - 1459 . DOI: 10.1038/s41590-024-01884-z http://doi.org/10.1038/s41590-024-01884-z

GLASNER A , LEVI A , ENK J , et al . NKp46 receptor-mediated interferon-γ production by natural killer cells increases fibronectin 1 to alter tumor architecture and control metastasis [J ] . Immunity , 2018 , 48 ( 1 ): 107 - 119 .e4. DOI: S1074-7613(17)30536-8 http://doi.org/S1074-7613(17)30536-8

HARMON C , ROBINSON M W , HAND F , et al . Lactate-mediated acidification of tumor microenvironment induces apoptosis of liver-resident NK cells in colorectal liver metastasis [J ] . Cancer Immunol Res , 2019 , 7 ( 2 ): 335 - 346 . DOI: 10.1158/2326-6066.CIR-18-0481 http://doi.org/10.1158/2326-6066.CIR-18-0481

DODARD G , TATA A , ERICK T K , et al . Inflammation-induced lactate leads to rapid loss of hepatic tissue-resident NK cells [J ] . Cell Rep , 2020 , 32 ( 1 ): 107855 DOI: 10.1016/j.celrep.2020.107855 http://doi.org/10.1016/j.celrep.2020.107855 https://linkinghub.elsevier.com/retrieve/pii/S2211124720308366 https://linkinghub.elsevier.com/retrieve/pii/S2211124720308366

ZHANG Y P , ZHONG F , LIU L . Single-cell transcriptional atlas of tumor-associated macrophages in breast cancer [J ] . Breast Cancer Res , 2024 , 26 ( 1 ): 129 . DOI: 10.1186/s13058-024-01887-6 http://doi.org/10.1186/s13058-024-01887-6

LIU N , LUO J , KUANG D , et al . Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2α-mediated tumor progression [J ] . J Clin Invest , 2019 , 129 ( 2 ): 631 - 646 . DOI: 10.1172/JCI123027 http://doi.org/10.1172/JCI123027

CAI Z N , LI W , HAGER S , et al . Targeting PHGDH reverses the immunosuppressive phenotype of tumor-associated macrophages through α-ketoglutarate and mTORC1 signaling [J ] . Cell Mol Immunol , 2024 , 21 ( 5 ): 448 - 465 . DOI: 10.1038/s41423-024-01134-0 http://doi.org/10.1038/s41423-024-01134-0

VADEVOO S M P , GUNASSEKARAN G R , LEE C , et al . The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages [J ] . Proc Natl Acad Sci USA , 2021 , 118 ( 37 ): e2102434118.

KHAN F , LIN Y Y , ALI H B , et al . Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression [J ] . Nat Commun , 2024 , 15 ( 1 ): 1987 . DOI: 10.1038/s41467-024-46193-z http://doi.org/10.1038/s41467-024-46193-z

LIU M Y , REN Y , ZHOU Z J , et al . The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia [J ] . Cancer Cell , 2024 , 42 ( 5 ): 885 - 903 .e4. DOI: 10.1016/j.ccell.2024.03.009 http://doi.org/10.1016/j.ccell.2024.03.009

JIANG R , REN W J , WANG L Y , et al . Targeting lactate: an emerging strategy for macrophage regulation in chronic inflammation and cancer [J ] . Biomolecules , 2024 , 14 ( 10 ): 1202 . DOI: 10.3390/biom14101202 http://doi.org/10.3390/biom14101202 https://www.mdpi.com/2218-273X/14/10/1202 https://www.mdpi.com/2218-273X/14/10/1202

SHU M , LU D C , ZHU Z Y , et al . Insight into the roles of lactylation in macrophages: functions and clinical implications [J ] . Clin Sci (Lond) , 2025 , 139 ( 2 ): 151 - 169 . DOI: 10.1042/CS20242737 http://doi.org/10.1042/CS20242737 https://portlandpress.com/clinsci/article/139/02/151/235606/Insight-into-the-roles-of-lactylation-in https://portlandpress.com/clinsci/article/139/02/151/235606/Insight-into-the-roles-of-lactylation-in

SUN J R , FENG Q M , HE Y , et al . Lactate activates CCL18 expression via H3K18 lactylation in macrophages to promote tumorigenesis of ovarian cancer [J ] . Acta Biochim Biophys Sin (Shanghai) , 2024 , 56 ( 9 ): 1373 - 1386 . DOI: 10.3724/abbs.2024111 http://doi.org/10.3724/abbs.2024111 https://www.sciengine.com/doi/10.3724/abbs.2024111 https://www.sciengine.com/doi/10.3724/abbs.2024111

SACHA M , FAUCON L , HAMON E , et al . Ex vivo transdermal absorption of a liposome formulation of diclofenac [J ] . Biomed Pharmacother , 2019 , 111 : 785 - 790 . DOI: 10.1016/j.biopha.2018.12.079 http://doi.org/10.1016/j.biopha.2018.12.079 https://linkinghub.elsevier.com/retrieve/pii/S0753332218352375 https://linkinghub.elsevier.com/retrieve/pii/S0753332218352375

LI X L , JIANG C , WANG Q H , et al . A “valve-closing” starvation strategy for amplification of tumor-specific chemotherapy [J ] . Adv Sci (Weinh) , 2022 , 9 ( 8 ): e2104671 .

BRESINSKY M , GOEPFERICH A . Control of biomedical nanoparticle distribution and drug release in vivo by complex particle design strategies [J ] . Eur J Pharm Biopharm , 2025 , 208 : 114634 . DOI: 10.1016/j.ejpb.2025.114634 http://doi.org/10.1016/j.ejpb.2025.114634 https://linkinghub.elsevier.com/retrieve/pii/S0939641125000104 https://linkinghub.elsevier.com/retrieve/pii/S0939641125000104

DING X L , LIU M D , CHENG Q , et al . Multifunctional liquid metal-based nanoparticles with glycolysis and mitochondrial metabolism inhibition for tumor photothermal therapy [J ] . Biomaterials , 2022 , 281 : 121369 . DOI: 10.1016/j.biomaterials.2022.121369 http://doi.org/10.1016/j.biomaterials.2022.121369 https://linkinghub.elsevier.com/retrieve/pii/S0142961222000084 https://linkinghub.elsevier.com/retrieve/pii/S0142961222000084

DUAN R X , XU Y Y , ZENG X M , et al . Uncovering the metabolic origin of aspartate for tumor growth using an integrated molecular deactivator [J ] . Nano Lett , 2021 , 21 ( 1 ): 778 - 784 . DOI: 10.1021/acs.nanolett.0c04520 http://doi.org/10.1021/acs.nanolett.0c04520

WANG D W , REN X H , MA Y J , et al . Dual-template epitope imprinted nanoparticles for anti-glycolytic tumor-targeted treatment [J ] . J Colloid Interface Sci , 2025 , 683 ( Pt 2 ): 890 - 905 .

FARAH C , NEVEU M A , BOUZIN C , et al . Hyperpolarized 13 C-pyruvate to assess response to anti-PD1 immune checkpoint inhibition in YUMMER 1.7 melanoma xenografts [J ] . Int J Mol Sci , 2023 , 24 ( 3 ): 2499 . DOI: 10.3390/ijms24032499 http://doi.org/10.3390/ijms24032499 https://www.mdpi.com/1422-0067/24/3/2499 https://www.mdpi.com/1422-0067/24/3/2499

ZHOU J R , HU Y P , CAO Y H , et al . A Lactate-Depleting metal organic framework-based nanocatalyst reinforces intratumoral T cell response to boost anti-PD1 immunotherapy [J ] . J Colloid Interface Sci , 2024 , 660 : 869 - 884 . DOI: 10.1016/j.jcis.2024.01.129 http://doi.org/10.1016/j.jcis.2024.01.129 https://linkinghub.elsevier.com/retrieve/pii/S002197972400136X https://linkinghub.elsevier.com/retrieve/pii/S002197972400136X

WANG H J , WU C H , TONG X W , et al . A biomimetic metal-organic framework nanosystem modulates immunosuppressive tumor microenvironment metabolism to amplify immunotherapy [J ] . J Control Release , 2023 , 353 : 727 - 737 . DOI: 10.1016/j.jconrel.2022.11.054 http://doi.org/10.1016/j.jconrel.2022.11.054 https://linkinghub.elsevier.com/retrieve/pii/S0168365922008082 https://linkinghub.elsevier.com/retrieve/pii/S0168365922008082

SOMCHOB B , PROMPHET N , RODTHONGKUM N , et al . Zwitterionic hydrogel for preserving stability and activity of oxidase enzyme for electrochemical biosensor [J ] . Talanta , 2024 , 270 : 125510 . DOI: 10.1016/j.talanta.2023.125510 http://doi.org/10.1016/j.talanta.2023.125510 https://linkinghub.elsevier.com/retrieve/pii/S0039914023012614 https://linkinghub.elsevier.com/retrieve/pii/S0039914023012614

CHOI H , YEO M , KANG Y J , et al . Lactate oxidase/catalase-displaying nanoparticles efficiently consume lactate in the tumor microenvironment to effectively suppress tumor growth [J ] . J Nanobiotechnology , 2023 , 21 ( 1 ): 5 . DOI: 10.1186/s12951-022-01762-6 http://doi.org/10.1186/s12951-022-01762-6

ZHAO S F , HOU J N , DENG L , et al . Lactate-modulating nanozyme-mediated mitochondrial respiration block for tumor immunosuppression remodeling [J ] . Angew Chem Int Ed , 2025 , 64 ( 17 ): e202422203.

ZHAO S F , LI H H , LIU R Y , et al . Nitrogen-centered lactate oxidase nanozyme for tumor lactate modulation and microenvironment remodeling [J ] . J Am Chem Soc , 2023 , 145 ( 18 ): 10322 - 10332 . DOI: 10.1021/jacs.3c02005 http://doi.org/10.1021/jacs.3c02005 https://pubs.acs.org/doi/10.1021/jacs.3c02005 https://pubs.acs.org/doi/10.1021/jacs.3c02005

NIE T Q , FANG Y F , ZHANG R H , et al . Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism [J ] . Bioact Mater , 2025 , 47 : 51 - 63 . DOI: 10.1016/j.bioactmat.2025.01.005 http://doi.org/10.1016/j.bioactmat.2025.01.005

MAO L Z , XARPIDIN B , SHI R , et al . Natural enzyme-loaded polymeric stealth coating-armed engineered probiotics by disrupting tumor lactate homeostasis to synergistic metabolism-immuno-enzyme dynamic therapy [J ] . Adv Sci (Weinh) , 2025 , 12 ( 16 ): e2417172 .

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