Blocking lactate: kick T cells when they are down-Immunometabolism-CSCIED科技核心评价数据库-手机版

Blocking lactate: kick T cells when they are down

Blocking lactate: kick T cells when they are down

ES评分 0 浏览量：219 下载量：0

DOI	10.1097/IN9.0000000000000059
刊名	Immunometabolism IJ
年，卷(期)	2025, 7(2)
作者	Horkova, Veronika; Everts, Bart; Brenner, Dirk,
作者单位	Luxembourg Inst Hlth, Dept Infect & Immun DII, Expt & Mol Immunol, Esch Sur Alzette, Luxembourg;
摘要	In the last couple of decades, cancer research has been shifting its focus to the immune system. Cancer cells, with their ability to adapt and evade immune responses, seem to accelerate the evolutionary pressure that has been put on our immune system during evolution. We thus try to aid these natural selection processes and assist our immune system to combat cancer. Here, we are discussing a study by Greg Delgoffe and colleagues that was published in Nature Immunology in December 2024, exploring a new approach to bring the dysfunctional immune cells back to life by blocking their lactate uptake.
Abstract	In the last couple of decades, cancer research has been shifting its focus to the immune system. Cancer cells, with their ability to adapt and evade immune responses, seem to accelerate the evolutionary pressure that has been put on our immune system during evolution. We thus try to aid these natural selection processes and assist our immune system to combat cancer. Here, we are discussing a study by Greg Delgoffe and colleagues that was published in Nature Immunology in December 2024, exploring a new approach to bring the dysfunctional immune cells back to life by blocking their lactate uptake.
关键词	T cell exhaustion; MCT11; lactate; hypoxia; metabolism; immune checkpoint blockade; anti-tumor immunity
KeyWord	T cell exhaustion; MCT11; lactate; hypoxia; metabolism; immune checkpoint blockade; anti-tumor immunity
基金项目
页码	-

参考文献
相关文献

[1]. Anderson KG, Stromnes IM, Greenberg PD. Obstacles posed by the tumor microenvironment to T cell activity: a case for synergistic therapies. Cancer Cell. 2017;31(3):311-25.

[2]. Guerra L, Bonetti L, Brenner D. Metabolic modulation of immunity: a new concept in cancer immunotherapy. Cell Rep. 2020;32(1):107848.

[3]. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486-99.

[4]. Miggelbrink AM, Jackson JD, Lorrey SJ, et al. CD4 T-cell exhaustion: does it exist and what are its roles in cancer? Clin Cancer Res. 2021;27(21):5742-52.

[5]. Scharping NE, Rivadeneira DB, Menk AV, et al. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat Immunol. 2021;22(2):205-15.

[6]. Utzschneider DT, Charmoy M, Chennupati V, et al. T cell factor 1-expressing memory-like CD8+ T cells sustain the immune response to chronic viral infections. Immunity. 2016;45(2):415-27.

[7]. Miller BC, Sen DR, Al Abosy R, et al. Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol. 2019;20(3):326-36.

[8]. Chi H. Immunometabolism at the intersection of metabolic signaling, cell fate, and systems immunology. Cell Mol Immunol. 2022;19(3):299-302.

[9]. Zheng Y, Delgoffe GM, Meyer CF, et al. Anergic T cells are metabolically anergic. J Immunol. 2009;183(10):6095-101.

[10]. Warburg OH. Über den stoffwechsel der tumoren: arbeiten aus dem Kaiser Wilheim-institute für biologie. Springer; 1926.

[11]. Watson MJ, Vignali PDA, Mullett SJ, et al. Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Nature. 2021;591(7851):645-51.

[12]. Liu W, Wang Y, Bozi LHM, et al. Lactate regulates cell cycle by remodelling the anaphase promoting complex. Nature. 2023;616(7958):790-7.

[13]. Raychaudhuri D, Singh P, Chakraborty B, et al. Histone lactylation drives CD8+ T cell metabolism and function. Nat Immunol. 2024;25(11):2140-51.

[14]. Bosshart PD, Charles R-P, Garibsingh R-AA, et al. SLC16 family: from atomic structure to human disease. Trends Biochem Sci. 2021;46(1):28-40.

[15]. Payen VL, Mina E, Van Hée VF, et al. Monocarboxylate transporters in cancer. Mol Metab. 2020;33:48-66.

[16]. Halford S, Veal GJ, Wedge SR, et al. A phase I dose-escalation study of AZD3965, an oral monocarboxylate transporter 1 inhibitor, in patients with advanced cancer. Clin Cancer Res. 2023;29(8):1429-39.

[17]. Bovenzi CD, Hamilton J, Tassone P, et al. Prognostic indications of elevated MCT4 and CD147 across cancer types: a meta-analysis. Biomed Res Int. 2015;2015:242437.

[18]. Peralta RM, Xie B, Lontos K, et al. Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism. Nat Immunol. 2024;25(12):2297-307.

[19]. Lee P, Chandel NS, Simon MC. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat Rev Mol Cell Biol. 2020;21(5):268-83.

[20]. Franchina DG, Dostert C, Brenner D. Reactive oxygen species: involvement in T Cell signaling and metabolism. Trends Immunol. 2018;39(6):489-502.

[21]. Mak TW, Grusdat M, Duncan GS, et al. Glutathione primes T cell metabolism for inflammation. Immunity. 2017;46(4):675-89.

[22]. Bonetti L, Horkova V, Longworth J, et al. A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation. Cell Metabol. 2024;36(8):1726-44.e10.

[23]. Yu Y-R, Imrichova H, Wang H, et al. Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion. Nat Immunol. 2020;21(12):1540-51.

[24]. Lv J, Zhou Z, Wang J, et al. Prognostic value of lactate dehydrogenase expression in different cancers: a meta-analysis. Am J Med Sci. 2019;358(6):412-21.

[25]. Kim W, Deik A, Gonzalez C, et al. Polyunsaturated fatty acid desaturation is a mechanism for glycolytic NAD+ recycling. Cell Metab. 2019;29(4):856-70.e7.

[26]. Brand A, Singer K, Koehl GE, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 2016;24(5):657-71.

引用本文

Horkova, Veronika; Everts, Bart; Brenner, Dirk. Blocking lactate: kick T cells when they are down [J]. Immunometabolism. 2025; 7; (2). - .

文献评论

相关学者

相关机构