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Low glucose availability potentiates the effects of metformin on model T cell activation and exhaustion markers in vitro [Elektronski vir]Repas, Jernej ...Modulation of immune cell metabolism is one of promising strategies to improve cancer immunotherapies. Metformin is an anti-diabetic drug with potential anti-cancer effects, ranging from ... normalization of blood glucose and insulin levels, direct anti-proliferative effects on cancer cells to emerging immunomodulatory effects on anti-tumor immunity. Metformin can reduce tumor hypoxia and PD-L1 expression, as well as normalize or improve T cell function and potentiate the effect of immune checkpoint inhibitors, making it a promising adjuvant to immunotherapy of tumors with poor response such as triple negative breast cancer (TNBC). However, although the effects of metformin on cancer cells are glucose-dependent, the role of glucose in modulating its effect on T cells has not been systematically studied. We thus investigated the effect of metformin as a function of glucose level on Jurkat cell and PBMC T cell models in vitro. While low metformin concentrations had little effect on T cell function, high concentration reduced proliferation and IFN-γ secretion in both models and induced a shift in T cell populations from memory to effector subsets. The PD-1/CD69 ratio was improved by high metformin in T cells from PBMC. Low glucose and metformin synergistically reduced PD-1 and CD69 expression and IFN-γ secretion in T cells from PBMC. Low glucose level itself suppressed Jurkat cell function due to their limited metabolic plasticity, but had limited effects on T cells from PBMC apart from reduced proliferation. Conversely, high glucose did not strongly affect either T cell model. Metformin in combination with glycolysis inhibitor 2-deoxy-D-glucose (2DG) reduced PD-1 in Jurkat cells, but also strongly suppressed their function. However, low, physiologically achievable 2DG concentration itself reduced PD-1 while mostly maintaining IL-2 secretion and, interestingly, even strongly increased IFN-γ secretion regardless of glucose level. Overall, glucose metabolism can importantly influence some of the effects of metformin on T cell functionality in the tumor microenvironment. Additionally, we show that 2DG could potentially improve the anti-tumor T cell response.Vir: Frontiers in endocrinology [Elektronski vir]. - ISSN 1664-2392 (Vol. 14, iss. , 2023, str. 1-24)Vrsta gradiva - e-članek ; neleposlovje za odrasleLeto - 2023Jezik - angleškiCOBISS.SI-ID - 177449219
Avtor
Repas, Jernej |
Peternel, Lea |
Sourij, Harald |
Pavlin, Mojca, 1973-
Teme
T cells |
metformin |
glucose level |
2-deoxy-D-glucose |
T cell exhaustion |
PD-1/PD-L1 axis |
T celice |
metformin |
raven glukoze |
izčrpanost T celic |
os PD-1/PD-L1
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Repas, Jernej | 50626 |
Peternel, Lea | 54183 |
Sourij, Harald | |
Pavlin, Mojca, 1973- | 19225 |
Vir: Osebne bibliografije
in: SICRIS
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