After prolonged extracorporeal multiplication in physiological culture media, there can be curative infusions of a cancer patient's own cytotoxic T cells (adoptive T cell transfer; ACT), which must achieve efficient activation in potentially adverse tumour microenvironments. With spectacular, yet irregular, success, improvements are needed. Developing lymphoid cells are biologically selected, not only for ‘near‐self’ reactivity (positive selection), but also to avoid self‐reactivity (negative selection). Thus, success requires harnessing near‐self cells while avoiding extreme autoimmune phenomena. Abrupt metabolic changes accompanying T cell activation to leave the G₀ stage and enter the G₁ stage of the cell cycle (eg enhanced glycolysis) are accompanied by increased transcription of the G0S9 gene that mediates salvage synthesis of NAD⁺ from nicotinamide; the latter has recently been shown to increase the efficiency of ACT. Despite theoretical and experimental advances, there has not been parallel progress in simulating in vivo conditions with culture media that were initially formulated for their positive benefits for tumour cell lines (cell survival and proliferation). Yet for lymphoid cells, inhibition or death (ie immunological tolerance) is as important as their activation and proliferation (immunological response). Thus, use of media optimized for the latter may mask the former. The resilience of established culture protocols may have been partly politically driven. However, unphysiological conditions have sometimes yielded fortuitous insights. Optimization of culture media for specific tissues must consider the nature of problems addressed in research settings and the need to avoid mishaps in clinical settings.

中文翻译：

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过继性T细胞转移癌免疫疗法的代谢优化：历史回顾。

在生理培养基中长时间体外繁殖后，可以治愈性注入癌症患者自身的细胞毒性T细胞（过继性T细胞转移； ACT），必须在潜在的不利肿瘤微环境中实现有效激活。要取得辉煌而又不定期的成功，就需要改进。从生物学上选择发育中的淋巴样细胞，不仅为了“自身”反应（阳性选择），而且还为了避免自身反应（阴性选择）。因此，成功需要利用附近的细胞，同时避免极端的自身免疫现象。伴随T细胞活化的突然代谢变化，离开G ₀期进入G ₁细胞周期的阶段（例如增强的糖酵解）伴随着G0S9基因转录的增加，该基因介导了从烟酰胺中NAD ^+的抢救合成。最近已证明后者可提高ACT的效率。尽管在理论和实验上取得了进步，但使用最初为它们的阳性反应而配制的培养基在模拟体内条件方面并没有取得平行进展。对肿瘤细胞系的好处（细胞存活和增殖）。然而对于淋巴样细胞，抑制或死亡（即免疫耐受）与其激活和增殖（免疫反应）一样重要。因此，使用为后者优化的媒体可能会掩盖前者。既定文化协议的复原力可能在某种程度上是由政治驱动的。但是，非生理条件有时会产生偶然的见解。针对特定组织的培养基的优化必须考虑研究环境中所解决问题的性质以及避免临床环境中不幸事故的需要。