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首页> 外文期刊>Journal of experimental & clinical cancer research : >Antitumor resistance activation in mice: can the immunological memory cells enhance resistance?
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Antitumor resistance activation in mice: can the immunological memory cells enhance resistance?

机译：小鼠抗肿瘤耐药性激活：免疫记忆细胞能否增强耐药性？

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Immunization of adult animals with the Ehrlich ascytic cancer cells homogenate three months prior to an experiment, did not affect either tumor transplantation or the progress of cancerogenesis induced by injection of 20-methylcholanthrene oil solution into the femoral muscle. All consequences of adult animal vaccination disappeared in 30-40 days following antigen administration. Quite different consequences were observed after immunization of the newborn mice. The same antigen (Ehrlich cancer cells homogenate) injected to newborn mice on days 1 and 3 after birth in a dose that failed to develop tolerance not only significantly increased the ascytic tumor transplantation threshold (by nearly 200 times for sarcoma 37 cells and by nearly 400 times for Ehrlich cancer cells) in adult animals but also led to almost 50% inhibition of cancerogenesis (induced by injection of 20-methylcholanthrene oil solution in the femoral muscle of mature mouse) after three and even after 12 months following immunization. The MTT-analysis did not reveal any noticeable differences in the number and activity of the cytotoxic lymphocytes in populations of splenocytes obtained from the intact mice (control) and from the adult animals which had been exposed to postnatal immunization (experiment).However, after a new vaccination such differences were found. In the populations of splenocytes obtained from control animals, the cytotoxic activity measured on day 10 after vaccination had increased 2.86-fold mainly at the expense of an increased number of effector cells. In the populations of splenocytes obtained from the experimental group of animals the activation was much greater (25.8-fold), being accomplished not only at the expense of an increased number of the effector cells, as observed in the control group, but also at the expense of their higher activity. The kinetic analysis of a mechanism of effector cells/target cells interaction has led to derive equations for estimation of the limiting rates of such interaction and of the equilibrium constants for interacting cells. Analysis of a generally accepted mechanism of the cytotoxic lymphocytes formation, with an account of the kinetic analysis data, has shown that a major reason of low antitumor resistance of animal organism is the negligible population of resting cells--the precursors of antitumor cytotoxic lymphocytes. Newborn mice vaccination does not produce any increase in the number of resting cells of the necessary type. This circumstance explains both, increase of the ascytic tumor transplantation threshold and increase of the resistance to 20-methylcholanthrene action in adulthood. Adult animal immunization does not possess such action. Analysis of the problem leads to the conclusion that the system of organism's antitumor resistance becomes effective only in those cases when, owing to antigen activation of resting cells, the concentration of cytotoxic lymphocytes rises to such an extent that the rate of tumor cell destruction becomes greater than the rate of target cells reproduction.
机译：在实验前三个月，用艾氏胆囊癌细胞对成年动物进行免疫接种均不会影响肿瘤移植或通过向股肌肉注射20甲基胆碱油溶液诱导的癌变进展。抗原施用后30-40天，成年动物疫苗接种的所有后果均消失了。新生小鼠免疫后观察到完全不同的结果。在出生后的第1天和第3天向新生小鼠注射相同的抗原（Ehrlich癌细胞匀浆），其剂量不能产生耐受性，不仅显着提高了囊性肿瘤移植阈值（肉瘤37细胞几乎增加了200倍，而肉瘤37细胞增加了近400倍）在免疫后三个月甚至12个月后，其成年动物体内的Ehrlich癌细胞数量减少了50％，但也导致了近50％的癌症发生抑制作用（由在成熟小鼠的股骨中注射20-甲基胆甾醇油溶液诱导）。 MTT分析未发现从完整小鼠（对照）和暴露于产后免疫（实验）的成年动物获得的脾细胞群体中细胞毒性淋巴细胞的数量和活性有任何显着差异。新的疫苗接种发现了这种差异。在得自对照动物的脾细胞群体中，接种疫苗后第10天测得的细胞毒性活性增加了2.86倍，主要是增加了效应细胞的数量。在从实验组动物获得的脾细胞群体中，激活要大得多（25.8倍），这不仅以对照组中观察到的效应细胞数量的增加为代价，而且在对照组中也是如此。牺牲他们较高的活动度。效应细胞/靶细胞相互作用机理的动力学分析导致​​导出方程式，用于估计这种相互作用的极限速率和相互作用细胞的平衡常数。通过对动力学分析数据的分析，对细胞毒性淋巴细胞形成的一种公认机制进行了分析，结果表明，动物生物体低抗肿瘤耐药性的主要原因是静止细胞的数量可忽略不计-抗肿瘤细胞毒性淋巴细胞的前体。新生小鼠接种疫苗不会增加必需类型的静息细胞数量。这种情况既可以解释成虫性肝癌移植阈值的提高，也可以解释其对成年期对20-甲基胆甾醇的抗药性的提高。成年动物免疫不具有这种作用。对问题的分析得出的结论是，仅在以下情况下，机体的抗肿瘤抗性系统才有效：由于静息细胞的抗原激活，细胞毒性淋巴细胞的浓度升高到某种程度，以致肿瘤细胞破坏的速率变得更大。比靶细胞繁殖的速度快。

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