更新于：2024-05-01

TOX

thymocyte selection associated high mobility group box

更新于：2024-05-01

基本信息

别名

KIAA0808、thymocyte selection associated high mobility group box、Thymocyte selection-associated high mobility group box protein TOX

+ [3]

简介

Transcriptional regulator with a major role in neural stem cell commitment and corticogenesis as well as in lymphoid cell development and lymphoid tissue organogenesis (By similarity). Binds to GC-rich DNA sequences in the proximity of transcription start sites and may alter chromatin structure, modifying access of transcription factors to DNA. During cortical development, controls the neural stem cell pool by inhibiting the switch from proliferative to differentiating progenitors. Beyond progenitor cells, promotes neurite outgrowth in newborn neurons migrating to reach the cortical plate. May activate or repress critical genes for neural stem cell fate such as SOX2, EOMES and ROBO2 (By similarity). Plays an essential role in the development of lymphoid tissue-inducer (LTi) cells, a subset necessary for the formation of secondary lymphoid organs: peripheral lymph nodes and Peyer's patches. Acts as a developmental checkpoint and regulates thymocyte positive selection toward T cell lineage commitment. Required for the development of various T cell subsets, including CD4-positive helper T cells, CD8-positive cytotoxic T cells, regulatory T cells and CD1D-dependent natural killer T (NKT) cells. Required for the differentiation of common lymphoid progenitors (CMP) to innate lymphoid cells (ILC) (By similarity). May regulate the NOTCH-mediated gene program, promoting differentiation of the ILC lineage. Required at the progenitor phase of NK cell development in the bone marrow to specify NK cell lineage commitment (PubMed:21126536) (By similarity). Upon chronic antigen stimulation, diverts T cell development by promoting the generation of exhaustive T cells, while suppressing effector and memory T cell programming. May regulate the expression of genes encoding inhibitory receptors such as PDCD1 and induce the exhaustion program, to prevent the overstimulation of T cells and activation-induced cell death (By similarity).

关联

100 项与 TOX 相关的临床结果

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100 项与 TOX 相关的转化医学

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0 项与 TOX 相关的专利（医药）

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798

项与 TOX 相关的文献（医药）

2024-02-15·Heliyon

HO-1 attenuates testicular ischaemia/reperfusion injury by activating the phosphorylated C-jun-miR-221/222-TOX pathway.

Article

作者: Bo Xie ; Bing Cheng ; Lugeng He ; Yunfu Liu ; Ning He

Aims:

Heme oxygenase (HO-1) affords protection against ischaemia/reperfusion (I/R) injury; however, its effects on testicular I/R injury remain poorly explored. Herein, we aimed to examine the effects of HO-1 on testicular I/R injury and elucidate the underlying mechanism.

Methods:

Using the TALEN technique, we knocked out the HO-1 gene from rats. In vivo: Thirty hmox+/+ and 30 hmox-/- rats were randomly assigned to six groups: sham-operated (sham), I/R (the left testicle torsion/detorsion) 0 d,I/R 1d, I/R 3d, I/R 7d and I/R 28d. In vitro: GC-1 were suffered from: control,H/R (oxygen-deprivation/reoxygenation),H/R + HO-1 siRNA,H/R + c-Jun siRNA or H/R + HO-1 siRNA + c-jun.We performed immunofluorescence and immunohistochemistry experiments to detect HO-1 nuclear translocation. Flow cytometry was used to detect cell apoptosis and analyse the cell cycle. High-resolution miRNA, mRNA sequencing, reverse transcription-quantitative PCR, and western blotting were performed to identify testicular I/R injury-related genes strongly conserved in HO-1 knockout rats. A double luciferase reporter assay was performed to verify the relationship between C-jun and miR-221/222.

Main findings:

In vivo, HO-1 improved the pathological damage induced by testicular I/R. In GC-1 cells, we confirmed the nuclear translocation of HO-1 and its protective effect against hypoxia/reoxygenation (H/R) damage. Accordingly, HO-1 protein itself, rather than heme metabolites, might play a key role in testicular I/R. Gene sequencing was performed to screen for miR221/222 and its downstream gene, thymocyte selection-associated high mobility group box (TOX). HO-1 increased c-Jun phosphorylation in the H/R group, knocked down c-Jun in GC-1 cells, and decreased miR-221/222 expression. Inhibition of HO-1 expression decreased the expression of c-Jun and miR-221/222, which was rescued by adding c-Jun. Dual-luciferase reporter assay confirmed the interaction between c-Jun and miR-221/222.

Conclusions:

HO-1 could exert a protective effect against testicular I/R via the phosphorylated c-Jun-miR-221/222-TOX pathway.

2024-01-31·Cancer immunology, immunotherapy : CII

Adipose-derived stem cell exosomes promote tumor characterization and immunosuppressive microenvironment in breast cancer.

Article

作者: Qin Zhu ; Yukun Cao ; Jiaqi Yuan ; Yu Hu

Adipose-derived stem cells (ASC) or autologous fat transplantation could be used to ameliorate breast cancer postoperative deformities. This study aims to explore the action of ASC and ASC-exosomes (ASC-exos) in breast cancer characterization and tumor microenvironment immunity, which provided a new method into the application of ASC-exos. ASC were extracted from human adipose tissue for the isolation and verification of ASC-exos. ASC-exos were co-cultured with CD4⁺T cells, CD14+ monocytes and MCF-7 cells, respectively. The tumor formation of nude mice was also constructed. Cell characterization was determined by CCK8, scratch assay, and Transwell. Hematoxylin-eosin (HE), immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to observe the histopathology and protein expression. CD4⁺T cell and CD14+ monocytes differentiation was detected by flow cytometry. Western blot, qRT-PCR and RNAseq were used to detect the action of ASC-exos on gene and protein expression. CD4⁺T cells could take up ASC-exos. ASC-exos inhibited Th1 and Th17 differentiation and promoted Treg differentiation of CD4⁺T cells. ASC-exos inhibited M1 differentiation and promoted M2 differentiation of CD14+ monocytes. ASC-exos promoted the migration, proliferation, and invasion, while inhibited apoptosis of MCF-7 cells. ASC-exos promoted the tumor formation of breast cancer. The effect of ASC-exos on tumor microenvironment immunity was in accordance with the above in vitro results. TOX, CD4 and LYZ1 genes were upregulated, while Mettl7b and Serpinb2 genes were downregulated in ASC-exos group. Human T-cell leukemia virus 1 infection pathway was significantly enriched in ASC-exos. Thus, ASC-exos promoted breast cancer characterization and tumor microenvironment immunosuppression by regulating macrophage and T cell differentiation.

2024-01-29·Journal of pharmaceutical and biomedical analysis

Carbon nanospheres dual spectral-overlapped fluorescence quenching lateral flow immunoassay for rapid diagnosis of toxoplasmosis in humans.

Article

作者: Xiaozhou Li ; Qi Wang ; Xintong Li ; Cong Wang ; Jinhui Lu ; Enhui Zhang ; Chaolan Liang ; Wenjing Wang ; Yongshui Fu ; Chengyao Li ; Ling Zhang ; Tingting Li

Toxoplasmosis is a common zoonotic disease caused by a protozoan parasite Toxoplasma gondii (Tox), approximately infecting one-third of human populations worldwide. This study developed the carbon nanospheres (CNPs) based dual spectral-overlapped fluorescence quenching lateral flow immunoassay (CNPs-FQLFIA) for detection of Tox antibodies (ToxAbs). The CNPs have been effectively coupled with Tox antigen (ToxAg), which can completely overlap the excitation and emission spectra of europium nanospheres (EuNPs) and CdSe/ZnS quantum dots (QDs) in testing strips of CNPs-QDs-FQLFIA or CNPs-EuNPs-FQLFIA. The sensitivity of CNPs-EuNPs-FQLFIA or CNPs-QDs-FQLFIA was 4 or 8 IU/mL under natural light readout, or both 4 IU/mL ToxAbs under ultraviolet (UV) light readout by the naked eyes, respectively. The limit of detection (LOD) of two types of CNPs-FQLFIA was both 1 IU/mL ToxAbs under UV light by a dry fluorescence analyzer, but no cross-reaction was found with other antibodies. The intra-assay coefficient variation (CV) of both CNPs-EuNPs-FQLFIA and CNPs-QDs-FQLFIA was less than 8%, while the inter-assay CV was less than 14%, respectively. The correlation coefficient (R²) of CNPs-EuNPs-FQLFIA or CNPs-QDs-FQLFIA to measure the different concentrations of ToxAbs spiked serum samples was 0.99712 and 0.99896, respectively. The CNPs-FQLFIA presented a characteristics of 94.3% sensitivity, 100% specificity and 98% accuracy for detection of ToxAbs in clinical serum samples. In conclusion, CNPs-FQLFIA with EuNPs or QDs fluorescence reporter was an easy, rapid, sensitive, precise and quantitative assay for detecting Tox antibodies in human blood samples.

项与 TOX 相关的新闻（医药）

2024-03-22

·生物谷

《细胞·代谢》：科学家揭示瘤内T细胞囤油不耗油、变身守油奴的机制！

这项研究填补了实体瘤浸润T细胞无法产生足够能量的知识空白，并首次提出ACC是阻碍T细胞在营养应激条件下持续发挥功能的分子开关。近日，一篇发表在《细胞代谢》期刊上的论文揭示[1]，深陷肿瘤当中的T细胞产不出能量，是因为自身的代谢“开关”被肿瘤改动，用于产能的脂肪囤成“肥肉”了！美国北卡罗来纳大学教堂山分校的Jessica E. Thaxton团队发现，肿瘤微环境中的代谢应激会导致T细胞中的乙酰辅酶A羧化酶（ACC）活性升高，这促使T细胞倾向于储存而非分解脂质，脂滴在T细胞中积累，脂肪酸氧化产生能量的代谢途径被抑制，阻碍了T细胞的有效功能。使用ACC抑制剂可以挽救T细胞的代谢，使其对脂肪的处理偏好于用来脂肪酸氧化而不是脂质储存，并增强T细胞的抗肿瘤效应、改善T细胞线粒体结构。这项研究填补了实体瘤浸润T细胞无法产生足够能量的知识空白，并首次提出ACC是阻碍T细胞在营养应激条件下持续发挥功能的分子开关。论文首页截图在这项研究中，Jessica E. Thaxton团队利用纤维肉瘤小鼠模型（MCA-205）、结直肠癌小鼠模型（MC-38）和黑色素瘤小鼠模型（B16）发现，相对于脾脏或淋巴结来源的CD8+T细胞，肿瘤浸润CD8+T细胞中与脂质代谢紊乱相关的基因富集，脂质积累增加大约1.5倍，大多数类别的脂质丰度都有提高。使用共聚焦显微镜可观察到，肿瘤浸润CD8+T细胞积累有相对更多的脂滴。随后的一系列结果表明，进入实体瘤肿瘤微环境是T细胞脂质积累的驱动因素。由于快速增殖的需求，肿瘤细胞大量消耗抢夺微环境中的葡萄糖、氧气等各种生存资源，这些压力、应激诱导了肿瘤浸润T细胞中脂滴的积累。更重要的是，他们发现，随着肿瘤发展，脂滴积累增加，脂滴浓度升高与肿瘤浸润CD8+T细胞功能障碍标志物PD-1、Tim-3、TOX、CTLA-4、LAG-3的表达上调相关。这些结果表明，肿瘤浸润CD8+T细胞中异常的脂质积累与起功能受损相关。肿瘤微环境驱动T细胞脂滴形成，且脂滴形成与T细胞功能受损相关 ACC是参与脂肪酸生物合成过程的关键代谢酶。ACC活性会导致脂肪酸合成增加，同时间接阻止线粒体将其利用进行脂肪酸氧化（FAO）来产生ATP。ACC可以说是细胞中的代谢开关，调节着脂质储存与脂质分解以获取能量之间的平衡，“如果ACC被‘打开’，细胞通常会储存脂质；如果 ACC‘关闭’，细胞则倾向于使用线粒体中的脂质来制造ATP，”Thaxton说[2]。肿瘤正是借着ACC给T细胞养起了膘。研究者们发现，CD8+T细胞在肿瘤微环境下被诱导ACC过度表达，这导致脂滴积累并限制脂肪酸水解，而脂肪酸水解是细胞在肿瘤微环境这样的营养限制条件下的重要能量产生途径。使用ACC抑制剂（ND-646）限制T细胞中ACC的活性，会显著改变T细胞代谢特征，导致T细胞的脂质合成减少、脂滴减少，促进T细胞将脂肪酸用于氧化分解并产生更多ATP。 ACC抑制剂对T细胞代谢大改造从功能上来看，ACC抑制剂处理后，CD8+T细胞表型重塑，被激活并扩增，与T细胞记忆性状相关的基因集富集而耗竭特征减弱，CD62L、TCF-1、BCL-2等干性生物标记物上调。此外，T细胞的线粒体结构得到改善，线粒体数量更多、体积更大，线粒体嵴以及线粒体与内质网接触点的数量也更多。将经过ACC抑制剂一番打造的T细胞输注给黑色素瘤小鼠，可以观察到小鼠T细胞在肿瘤微环境中持续发挥抗肿瘤功能，输注第七天时，肿瘤微环境中具有活性的CD8+T细胞占比相较于对照组增加3倍，干性相关的转录因子表达上调；与对照组相比，小鼠肿瘤进展得到更有效控制。不仅如此，研究者们获取7名健康捐献者的外周T细胞进行评估和体外培养发现，ACC抑制剂处理可以促进记忆T细胞的形成。 ACC抑制剂增加T细胞抗肿瘤功能和干性表型也就是说，ACC抑制剂能够改善了T细胞在肿瘤微环境中的代谢状态和抗肿瘤功能，这项研究成果可能有助于增强CAR-T细胞疗法，从患者体内取出T细胞经体外修饰和ACC抑制剂处理后，重新输注患者体内以对抗癌症。对于研究结果，Jessica E. Thaxton猜想，T细胞可能是需要脂质的“微妙平衡”才能在实体瘤中持续存在，不仅得有足够的脂质以提供能量来对抗癌细胞，还要控制脂质的积累，以避免过多的脂质储存对其功能产生负面影响。未来的工作中，Jessica E. Thaxton团队将进一步尝试CAR-T细胞疗法以外的应用，即能否绕开取出T细胞再输注这一过程，直接在患者肿瘤翻转T细胞的ACC代谢开关。但是在这之前，还得确定调节ACC开关对其它免疫细胞有何影响。参考文献： [1] Hunt, E. G., Hurst, K. E., Riesenberg, B. P., Kennedy, A. S., Gandy, E. J., Andrews, A. M., Del Mar Alicea Pauneto, C., Ball, L. E., Wallace, E. D., Gao, P., Meier, J., Serody, J. J., Coleman, M. F., & Thaxton, J. E. (2024). Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment. Cell metabolism, S1550-4131(24)00055-X. Advance online publication. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.cmet.2024.02.009 [2]https://news.unchealthcare.org/2024/03/researchers-gain-insight-into-why-t-cells-lose-energy-in-solid-tumors/

细胞疗法免疫疗法

2024-03-20

·奇点网

肿瘤在暗中促使T细胞“养肥膘”！

*仅供医学专业人士阅读参考T细胞被寄予众望为肿瘤细胞的“杀手”。可在实战过程中，浸润在实体瘤肿瘤微环境中的T细胞往往不给力，呈现代谢受损状态，其特点是无法合成足够的能量以维持抗肿瘤功能和自身生存。近日，一篇发表在《细胞代谢》期刊上的论文揭示[1]，深陷肿瘤当中的T细胞产不出能量，是因为自身的代谢“开关”被肿瘤改动，用于产能的脂肪囤成“肥肉”了！美国北卡罗来纳大学教堂山分校的Jessica E. Thaxton团队发现，肿瘤微环境中的代谢应激会导致T细胞中的乙酰辅酶A羧化酶（ACC）活性升高，这促使T细胞倾向于储存而非分解脂质，脂滴在T细胞中积累，脂肪酸氧化产生能量的代谢途径被抑制，阻碍了T细胞的有效功能。使用ACC抑制剂可以挽救T细胞的代谢，使其对脂肪的处理偏好于用来脂肪酸氧化而不是脂质储存，并增强T细胞的抗肿瘤效应、改善T细胞线粒体结构。这项研究填补了实体瘤浸润T细胞无法产生足够能量的知识空白，并首次提出ACC是阻碍T细胞在营养应激条件下持续发挥功能的分子开关。论文首页截图在这项研究中，Jessica E. Thaxton团队利用纤维肉瘤小鼠模型（MCA-205）、结直肠癌小鼠模型（MC-38）和黑色素瘤小鼠模型（B16）发现，相对于脾脏或淋巴结来源的CD8+T细胞，肿瘤浸润CD8+T细胞中与脂质代谢紊乱相关的基因富集，脂质积累增加大约1.5倍，大多数类别的脂质丰度都有提高。使用共聚焦显微镜可观察到，肿瘤浸润CD8+T细胞积累有相对更多的脂滴。随后的一系列结果表明，进入实体瘤肿瘤微环境是T细胞脂质积累的驱动因素。由于快速增殖的需求，肿瘤细胞大量消耗抢夺微环境中的葡萄糖、氧气等各种生存资源，这些压力、应激诱导了肿瘤浸润T细胞中脂滴的积累。更重要的是，他们发现，随着肿瘤发展，脂滴积累增加，脂滴浓度升高与肿瘤浸润CD8+T细胞功能障碍标志物PD-1、Tim-3、TOX、CTLA-4、LAG-3的表达上调相关。这些结果表明，肿瘤浸润CD8+T细胞中异常的脂质积累与起功能受损相关。肿瘤微环境驱动T细胞脂滴形成，且脂滴形成与T细胞功能受损相关ACC是参与脂肪酸生物合成过程的关键代谢酶。ACC活性会导致脂肪酸合成增加，同时间接阻止线粒体将其利用进行脂肪酸氧化（FAO）来产生ATP。ACC可以说是细胞中的代谢开关，调节着脂质储存与脂质分解以获取能量之间的平衡，“如果ACC被‘打开’，细胞通常会储存脂质；如果 ACC‘关闭’，细胞则倾向于使用线粒体中的脂质来制造ATP，”Thaxton说[2]。肿瘤正是借着ACC给T细胞养起了膘。研究者们发现，CD8+T细胞在肿瘤微环境下被诱导ACC过度表达，这导致脂滴积累并限制脂肪酸水解，而脂肪酸水解是细胞在肿瘤微环境这样的营养限制条件下的重要能量产生途径。使用ACC抑制剂（ND-646）限制T细胞中ACC的活性，会显著改变T细胞代谢特征，导致T细胞的脂质合成减少、脂滴减少，促进T细胞将脂肪酸用于氧化分解并产生更多ATP。ACC抑制剂对T细胞代谢大改造从功能上来看，ACC抑制剂处理后，CD8+T细胞表型重塑，被激活并扩增，与T细胞记忆性状相关的基因集富集而耗竭特征减弱，CD62L、TCF-1、BCL-2等干性生物标记物上调。此外，T细胞的线粒体结构得到改善，线粒体数量更多、体积更大，线粒体嵴以及线粒体与内质网接触点的数量也更多。将经过ACC抑制剂一番打造的T细胞输注给黑色素瘤小鼠，可以观察到小鼠T细胞在肿瘤微环境中持续发挥抗肿瘤功能，输注第七天时，肿瘤微环境中具有活性的CD8+T细胞占比相较于对照组增加3倍，干性相关的转录因子表达上调；与对照组相比，小鼠肿瘤进展得到更有效控制。不仅如此，研究者们获取7名健康捐献者的外周T细胞进行评估和体外培养发现，ACC抑制剂处理可以促进记忆T细胞的形成。ACC抑制剂增加T细胞抗肿瘤功能和干性表型也就是说，ACC抑制剂能够改善了T细胞在肿瘤微环境中的代谢状态和抗肿瘤功能，这项研究成果可能有助于增强CAR-T细胞疗法，从患者体内取出T细胞经体外修饰和ACC抑制剂处理后，重新输注患者体内以对抗癌症。对于研究结果，Jessica E. Thaxton猜想，T细胞可能是需要脂质的“微妙平衡”才能在实体瘤中持续存在，不仅得有足够的脂质以提供能量来对抗癌细胞，还要控制脂质的积累，以避免过多的脂质储存对其功能产生负面影响。未来的工作中，Jessica E. Thaxton团队将进一步尝试CAR-T细胞疗法以外的应用，即能否绕开取出T细胞再输注这一过程，直接在患者肿瘤翻转T细胞的ACC代谢开关。但是在这之前，还得确定调节ACC开关对其它免疫细胞有何影响。参考文献：[1] Hunt, E. G., Hurst, K. E., Riesenberg, B. P., Kennedy, A. S., Gandy, E. J., Andrews, A. M., Del Mar Alicea Pauneto, C., Ball, L. E., Wallace, E. D., Gao, P., Meier, J., Serody, J. J., Coleman, M. F., & Thaxton, J. E. (2024). Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment. Cell metabolism, S1550-4131(24)00055-X. Advance online publication. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.cmet.2024.02.009[2]https://news.unchealthcare.org/2024/03/researchers-gain-insight-into-why-t-cells-lose-energy-in-solid-tumors/本文作者丨张艾迪

细胞疗法免疫疗法

2024-02-20

·今日头条

铁死亡新发现！中国医学科学院等团队合作发现最新抗肿瘤免疫治疗策略

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：癌细胞发展多种策略来逃避T细胞介导的杀伤。一方面，癌细胞可能会优先依赖某些氨基酸进行快速生长和转移。另一方面，足够的营养物质供应和摄取对于在肿瘤微环境（TME）中发挥有效的T细胞抗肿瘤反应是必要的。 2月15日，中国医学科学院苏州系统医学研究所张连军、苏州大学附属第二医院张力元和西安交通大学基础医学院张保军共同通讯在期刊《Cell Death & Disease》上在线发表题为“Cystine deprivation triggers CD36-mediated ferroptosis and dysfunction of tumor infiltrating CD8+T cells”的研究论文，研究结果揭示了肿瘤细胞对胱氨酸的竞争导致T细胞免疫功能受损。研究人员阐明了肿瘤浸润T细胞中铁死亡的新机制：胱氨酸匮乏导致谷氨酸积累，进而加剧CD36介导的脂质过氧化物产生。这些发现为靶向氨基酸代谢或CD36阻断的免疫治疗策略提供了理论基础。研究人员证明提高Gclc表达能保护T细胞免受胱氨酸匮乏引起的损伤，为改造T细胞以实现有效的抗肿瘤免疫治疗提供了潜在策略。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-06503-1 研究背景 01 过继性T细胞转移和免疫检查点阻断已经在某部分癌症患者中取得了持久的临床效果，但大多数患者由于高度免疫抑制的肿瘤微环境（TME），无法从这些治疗中获益，这对于有效治疗实体肿瘤的免疫疗法构成了重大挑战。在TME中，多种因素导致免疫抑制，包括低氧和pH水平、有限的营养物质供应（如葡萄糖、脂肪酸和氨基酸）、免疫抑制代谢产物积累（如ROS、乳酸和脂质）以及免疫抑制性细胞因子和趋化因子的增加分泌。在这方面，T细胞逐渐失去记忆或干细胞特性的能力，并向衰竭和功能障碍的方向分化。这表现为TCF1、LY108和CD62L的表达减少，以及PD-1、TIM-3和TOX等衰竭标志物水平升高。研究发现 02 在这项研究中，研究人员证明CD8+T细胞无法与肿瘤细胞竞争胱氨酸摄取，导致胱氨酸饥饿。胱氨酸匮乏诱导氧化应激和谷氨酸积累，从而上调CD36介导的脂质摄取。这个过程导致T细胞耗竭和铁死亡，表现为TCF1、LY108和CD62L表达的减少，伴随PD-1和TIM-3表达的增加，氧化应激和脂质积累的增加。胱氨酸匮乏的T细胞的细胞因子分泌，包括IFNγ、TNFα和IL-2，也有所下降。为了改善胱氨酸饥饿下T细胞的抗肿瘤能力，研究人员构建了表达谷胱甘肽合成限速酶Gclc的T细胞。Gclc是细胞内抗氧化剂的关键调节因子，最近的研究报告显示它通过消耗胱氨酸缺乏的肿瘤细胞中的谷氨酸来对抗铁死亡。这些观察结果暗示了Gclc在缺乏胱氨酸的TME下保护T细胞存活和功能的潜力。Gclc过表达通过谷胱甘肽合成和谷氨酸消耗增强T细胞的抗肿瘤功能。研究发现揭示了肿瘤在肿瘤微环境中诱导免疫抑制的新机制，并强调通过调节胱氨酸的可用性来提升T细胞的抗肿瘤免疫治疗潜力。研究结果 03 综上所述，研究结果揭示了肿瘤细胞对胱氨酸的竞争导致T细胞免疫功能受损。研究人员阐明了肿瘤浸润T细胞中铁死亡的新机制：胱氨酸匮乏导致谷氨酸积累，进而加剧CD36介导的脂质过氧化物产生。这些发现为靶向氨基酸代谢或CD36阻断的免疫治疗策略提供了理论基础。研究人员证明提高Gclc表达能保护T细胞免受胱氨酸匮乏引起的损伤，为改造T细胞以实现有效的抗肿瘤免疫治疗提供了潜在策略。参考资料： https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-06503-1 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！点击对应文字查看详情

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