The inhibition of CD4 + T cell proinflammatory response by lactic acid is independent of Monocarboxylate transporter 1

2021 ◽  
Author(s):  
Peng Yang ◽  
Ying Sun ◽  
Min Zhang ◽  
Linhan Hu ◽  
Xinwei Wang ◽  
...  
Keyword(s):  
Lactic Acid ◽  
T Cell ◽  
Cd4 T Cell ◽  
Monocarboxylate Transporter ◽  
Proinflammatory Response ◽  
Monocarboxylate Transporter 1

scholarly journals Immunohistochemical Evaluation and Prognostic Value of Monocarboxylate Transporter 1 (MCT1) and 4 (MCT4) in T-cell Non-Hodgkin Lymphoma

2021 ◽  
Author(s):  
Hu Zhao ◽  
Yuan Chen ◽  
You-Ping Liao ◽  
Hai-Mei Chen ◽  
Qiu-Hong Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Value ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Monocarboxylate Transporter ◽  
Disease Stage ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
Monocarboxylate Transporter 1

Abstract Tumor cells often exhibit the Warburg effect, wherein, they preferentially undergo glycolysis over oxidative phosphorylation for energy production. Monocarboxylate transporter 1 (MCT1) and 4 (MCT4) are critical symporters mediating lactate efflux and preventing intracellular acidification during tumor growth. Numerous studies have focused on inhibiting MCT1 or MCT4 in various cancers. However, its role in T-cell lymphoma (TCL) is not yet investigated owing to the low incidence of TCL. This study was designed to investigate the expression of MCT1/MCT4 in patients with TCL and determine their prognostic value in this cancer. We performed immunohistochemistry to evaluate the expression level of MCT1/MCT4 in 38 TCL tissue samples and then compared their expression among different TCL subgroups, which were formed based on different clinical characteristics. Survival analysis was performed to evaluate the relationship between MCT1/MCT4 expression and both overall survival (OS) and progression-free survival (PFS). Our results revealed that MCT1 and MCT4 expression was significantly increased in TCL tissues compared to the control group. In addition, increased MCT1 expression associated with the female sex, advanced disease stage, increased serum LDH, Ki-67 at ≥50%, and intermediate or high-risk groups as categorized by the International Prognostic Index (IPI) score. We also found that increased MCT1 expression may be associated with reduced OS and PFS. In conclusion, MCT1 and MCT4 are overexpressed in patients with TCL, and may predict poor prognosis. MCT1 inhibition might be a novel treatment strategy for TCL, and further preclinical trials are required.

scholarly journals Gut derived lactic acid bacteria induce strain specific CD4+ T cell responses in human PBMC

2011 ◽  
Vol 30 (6) ◽  
pp. 845-851 ◽  
Author(s):  
Sytze de Roock ◽  
Merel van Elk ◽  
Maarten O. Hoekstra ◽  
Berent J. Prakken ◽  
Ger T. Rijkers ◽  
...  
Keyword(s):  
Lactic Acid ◽  
T Cell ◽  
Lactic Acid Bacteria ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Human Pbmc ◽  
Cell Responses

scholarly journals The Effects of Physical Exertion According to the Monocarboxylate Transporter 1 (MCT1) on the Speed of Lactic Acid Elimination in Futsal Players

2021 ◽  
Vol 11 (1) ◽  
pp. 80-87
Author(s):  
Mustafa Jassim Abd Zaed ◽  
◽  
Shimal H. Hamad Chomani ◽  
Marko Joksimovic ◽  
◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Lactic Acid ◽  
Lactic Acid Production ◽  
Physical Exertion ◽  
Middle Level ◽  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1 ◽  
Low Level ◽  
Sports Club ◽  
High Level

To identify the genetic diversity of futsal players in Al Hilla Sports Club for the season (2020-2021) after they were exposed to physical exertion by testing lactic mlss in the speed of recovery and elimination of lactic acid. The main experiment included two phases. The first is knowledge of the genetic diversity of the players. The first advanced level of this gene reached (5 players), the middle level (4 players), and the low level of the gene (3 players), and the second stage Of the experiment is to measure the searched variable (lactic acid) for all levels of the gene and to detect players who have a rapid elimination of lactic acid products. The experiment lasted for (2 months) and the most important conclusions were the high level of the MCT1 gene, the speed of elimination of lactic acid in the working muscles. There is a discrepancy between the hospitalization and the exercises. It appeared that the players who belong to this level have slow recovery Very compared to other levels, and this indicates that they are tired quickly. The players of this level have the advantage of quickly getting rid of lactic acid and recovering recovery compared to the low level, and they show less fatigue than the low level. The speed of elimination of lactic acid is less than the speed of its production, which facilitates the transfer of lactate from the working muscle to the blood and speed to get rid of it. Increasingly intense physical exertion affects the variation in the MCT1 gene level. The players at the high level of the MCT 1 gene showed an advantage in the speed of elimination of lactic acid production compared to the low and medium levels.

scholarly journals Lactic Acid Permeability of Aquaporin-9 Enables Cytoplasmic Lactate Accumulation via an Ion Trap

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 120
Author(s):  
Katharina Geistlinger ◽  
Jana D. R. Schmidt ◽  
Eric Beitz
Keyword(s):  
Lactic Acid ◽  
Ion Trap ◽  
Monocarboxylate Transporter ◽  
Acid Uptake ◽  
Monocarboxylate Transporter 1 ◽  
Low Concentrations ◽  
Aquaporin 9 ◽  
Uptake Rates ◽  
Ph Conditions ◽  
External Ph

(1) Background: Human aquaporin-9 (AQP9) conducts several small uncharged metabolites, such as glycerol, urea, and lactic acid. Certain brain tumors were shown to upregulate AQP9 expression, and the putative increase in lactic acid permeability was assigned to severity. (2) Methods: We expressed AQP9 and human monocarboxylate transporter 1 (MCT1) in yeast to determine the uptake rates and accumulation of radiolabeled l-lactate/l-lactic acid in different external pH conditions. (3) Results: The AQP9-mediated uptake of l-lactic acid was slow compared to MCT1 at neutral and slightly acidic pH, due to low concentrations of the neutral substrate species. At a pH corresponding to the pKa of l-lactic acid, uptake via AQP9 was faster than via MCT1. Substrate accumulation was fundamentally different between AQP9 and MCT1. With MCT1, an equilibrium was reached, at which the intracellular and extracellular l-lactate/H+ concentrations were balanced. Uptake via AQP9 was linear, theoretically yielding orders of magnitude of higher substrate accumulation than MCT1. (4) Conclusions: The selectivity of AQP9 for neutral l-lactic acid establishes an ion trap for l-lactate after dissociation. This may be physiologically relevant if the transmembrane proton gradient is steep, and AQP9 acts as the sole uptake path on at least one side of a polarized cell.

Inhibitory effect of tumor cell–derived lactic acid on human T cells

Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 3812-3819 ◽  
Author(s):  
Karin Fischer ◽  
Petra Hoffmann ◽  
Simon Voelkl ◽  
Norbert Meidenbauer ◽  
Julia Ammer ◽  
...  
Keyword(s):  
T Cells ◽  
Lactic Acid ◽  
Cytokine Production ◽  
Lactic Acid Production ◽  
Recovery Period ◽  
Monocarboxylate Transporter ◽  
Immune Functions ◽  
Tumor Spheroids ◽  
Activated T Cells ◽  
Monocarboxylate Transporter 1

Abstract A characteristic feature of tumors is high production of lactic acid due to enhanced glycolysis. Here, we show a positive correlation between lactate serum levels and tumor burden in cancer patients and examine the influence of lactic acid on immune functions in vitro. Lactic acid suppressed the proliferation and cytokine production of human cytotoxic T lymphocytes (CTLs) up to 95% and led to a 50% decrease in cytotoxic activity. A 24-hour recovery period in lactic acid–free medium restored CTL function. CTLs infiltrating lactic acid–producing multicellular tumor spheroids showed a reduced cytokine production. Pretreatment of tumor spheroids with an inhibitor of lactic acid production prevented this effect. Activated T cells themselves use glycolysis and rely on the efficient secretion of lactic acid, as its intracellular accumulation disturbs their metabolism. Export by monocarboxylate transporter-1 (MCT-1) depends on a gradient between cytoplasmic and extracellular lactic acid concentrations and consequently, blockade of MCT-1 resulted in impaired CTL function. We conclude that high lactic acid concentrations in the tumor environment block lactic acid export in T cells, thereby disturbing their metabolism and function. These findings suggest that targeting this metabolic pathway in tumors is a promising strategy to enhance tumor immunogenicity.

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