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The immunomodulatory effect of lactic acid within the tumor microenvironment
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Wei-xiang GE, Shi-jia YAN, Guo-hui WAN*
Acta Pharmaceutica Sinica | 2022, 57(9) : 2570 - 2579
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Acta Pharmaceutica Sinica | 2022, 57(9): 2570-2579
Special Reports: Therapeutic interventions and strategies for cancer immunotherapy
The immunomodulatory effect of lactic acid within the tumor microenvironment
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Wei-xiang GE, Shi-jia YAN, Guo-hui WAN*
Affiliations
  • School of Pharmaceutical Science, Sun Yat-san University, Guangzhou 510006, China
Published: 2022-09-12 doi: 10.16438/j.0513-4870.2022-0519
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Tumor cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate even under the circumstance of abundant oxygen. This phenomenon of aerobic glycolysis is known as the Warburg effect. Lactic acid, as an important tool for tumor cells to modify the tumor microenvironment, promotes the process of tumor invasion and metastasis, and contributes to tumor development by inducing and recruiting immunosuppression-related cells and molecules. Lactic acid could efflux out of the cancer cells via the monocarboxylate transporters to prevent intracellular acidification. Lactate can inhibit the cytolytic activity of T cells and natural killer (NK) cells, promoting the differentiation of tolerogenic interleukin 10 (IL-10)-producing dendritic cells. Moreover, the lactate-derived lactylation of histone lysine residues can promote macrophage polarization toward the M2-like phenotype, suppressing the immune response within the tumor microenvironment. In this review, we discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion from the aspects of lactic acid metabolism and its effect on immune cells. And we explore the possibility of targeting potential targets in lactate metabolism for tumor treatment. At last, we proposed a tumor immunotherapy strategy by inhibiting the pathway of aerobic glycolysis and proteins associated with the production and transport of lactic acid.

lactic acid  /  tumor microenvironment  /  immune system  /  epigenomics  /  glycolysis
Wei-xiang GE, Shi-jia YAN, Guo-hui WAN. The immunomodulatory effect of lactic acid within the tumor microenvironment[J]. Acta Pharmaceutica Sinica, 2022 , 57 (9) : 2570 -2579 . DOI: 10.16438/j.0513-4870.2022-0519
Year 2022 volume 57 Issue 9
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doi: 10.16438/j.0513-4870.2022-0519
  • Receive Date:2022-04-29
  • Online Date:2025-12-24
  • Published:2022-09-12
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  • Received:2022-04-29
  • Revised:2022-05-18
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    School of Pharmaceutical Science, Sun Yat-san University, Guangzhou 510006, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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