CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Time-dependent changes in the glycolytic pathway in activated T cells are independent of tumor burden or anti-cancer chemotherapy.
Time-dependent changes in the glycolytic pathway in activated T cells are independent of tumor burden or anti-cancer chemotherapy.
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尽管活化的过继性T细胞疗法(ATC)是一种有效的癌症治疗方法,但T细胞活化的调控如何影响其生化特征尚不清楚,而后者显著影响细胞功能。
本研究旨在探讨在多克隆活化对不同化疗治疗设置下荷瘤小鼠T细胞代谢特征的影响。三十只雌性Swiss白化小鼠分为5组(n = 6/每组),Gp1(PBS),Gp2组腹腔注射(i.p)1 × 106个细胞/只Ehrlich腹水癌(EAC),Gp3-Gp5组用顺铂(20 mg/只)治疗,分别表示为EAC/CIS/1wk或EAC/CIS/2wk,每隔一天给药3次。脾细胞在存在或不存在刀豆蛋白A(Con-A)和IL-2的条件下培养24 h或72 h,然后收获细胞,并处理以测定己糖激酶(HK)、磷酸果糖激酶(PFK)、乳酸脱氢酶(LDH)和葡萄糖6磷酸脱氢酶(G6PD)的酶活性。
结果显示,在培养前,从EAC/PBS/1wk小鼠或接种EAC/CIS/1wk小鼠中收获的T细胞,其HK、PFK、LDH和G6PH活性高于naive T细胞。在培养和活化24 h和72 h后,从EAC/CIS/2wk小鼠或EAC/CIS/3wk小鼠中收获的T细胞酶活性较其对照降低。未接受化疗的肿瘤晚期阶段糖酵解速率较低。在晚期活化中,naive和接受化疗的肿瘤早期阶段可产生高糖酵解代谢。这些结果对于过继性T细胞疗法的应用具有重要意义。
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.
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