Time-dependent changes in the glycolytic pathway in activated T cells are independent of tumor burden or anti-cancer chemotherapy

•In resting lymphocyte, the activity of cells is low, therefore, the level of glucose is decreased, concomitant with a high level of G6P, HKase, PFKase and low levels of LDH and G6PD.•The activation of T-lymphocytes whether by antigen (tumor/chemotherapy) or by Con– A/IL2.•Short activation naive and...

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Veröffentlicht in:International immunopharmacology 2023-09, Vol.122, p.110622-110622, Article 110622
Hauptverfasser: Khalil, Sohaila M., Eltaramsy, Asmaa, Hegazi, Mona M., Mohamed, Tarek M., Alwasel, Saleh, Salem, Mohamed L.
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Sprache:eng
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Zusammenfassung:•In resting lymphocyte, the activity of cells is low, therefore, the level of glucose is decreased, concomitant with a high level of G6P, HKase, PFKase and low levels of LDH and G6PD.•The activation of T-lymphocytes whether by antigen (tumor/chemotherapy) or by Con– A/IL2.•Short activation naive and early stage of tumor with or without chemotherapy can give high glycolic rate. However, late stage of tumor without chemotherapy gives low glycolic rate.•In late activation naive and early stage of tumor with chemotherapy can give high glycolic metabolism. These results are one of great importance application of adaptive T cell therapy. Although activated adoptive T cells therapy (ATC) is an effective approach for cancer treatment, it is not clear how modulation of T cell activation impacts their biochemical signature which significantly impacts the cell function. This study is aimed to investigate the impact of polyclonal activation on the metabolic signature of T cells from tumor-bearing mice under different settings of treatment with chemotherapy. Thirty female Swiss albino mice were divided into 5 groups (n = 6/each), Gp1(PBS), groups Gp2 were inoculated intraperitoneal (i.p) with 1 × 106 cells/mouse Ehrlich ascites carcinoma (EAC), Gp3-Gp5 were treated with cisplatin (20 mg/mice) which were represented as EAC/CIS/1wk Or EAC/CIS/2wk 3 times every other day. Splenocytes were cultured in or presence of concanavalin-A (Con-A) and IL-2 for 24 h or 72 h, then cells were harvested, and processed to determine the enzyme activities of hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and glucose 6 phosphate dehydrogenase(G6PD) enzymes. The results showed that before culture, T cells harvested from EAC/PBS/1wk of mice or inoculated with EAC/CIS/1wk showed higher activity in HK, PFK, LDH, and G6PH as compared to naive T cells. After 24, and 72 h of culture and activation, the enzyme activities in T cells harvested from EAC/CIS/2wk mice or EAC/CIS/3wk mice decreased compared with their control. The late stage of the tumor without chemotherapy gives a low glycolic rate. In late activation, naive and early stages of the tumor with chemotherapy can give high glycolic metabolism. These results show great significance as an application of adoptive T-cell therapy.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2023.110622