Invariant NKT cells metabolically adapt to the acute myeloid leukaemia environment.
Invariant NKT cells metabolically adapt to the acute myeloid leukaemia environment.
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DOI：
10.1007/s00262-022-03268-4
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发表时间：
2023-03
影响因子：
5.8
通讯作者：
De Santo, Carmela
中科院分区：
文献类型：
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作者：
Stavrou, Victoria;Fultang, Livingstone;Booth, Sarah;De Simone, Daniele;Bartnik, Arekdiusz;Scarpa, Ugo;Gneo, Luciana;Panetti, Silvia;Potluri, Sandeep;Almowaled, Meaad;Barlow, Jonathan;Jankevics, Andris;Lloyd, Gavin;Southam, Andrew;Priestman, David A.;Cheng, Paul;Dunn, Warwick;Platt, Frances;Endou, Hitoshi;Craddock, Charles;Keeshan, Karen;Mussai, Francis;De Santo, Carmela
急性髓系白血病(AML)通过精氨酸酶2(ARG2)诱导的精氨酸耗竭，为常规T细胞创造免疫抑制环境。我们发现AML细胞释放急性时相蛋白血清淀粉样蛋白A(SAA)，它以自分泌的方式上调ARG2的表达和活性，并促进AML原始细胞的生存。在体外串扰后，不变自然杀伤T细胞(INKT)被激活，上调线粒体能力，释放干扰素-γ。INKT在低精氨酸的急性髓系白血病环境中仍保持增殖和激活的能力，这是由于依赖于精氨酸琥珀酸合成酶1(ASS)的大分子氨基酸转运蛋白-1(LAT-1)和精氨酸琥珀酸合成酶1(ASS)依赖的氨基酸通路上调，导致AML细胞死亡。T细胞的增殖在体外和体内都得到了恢复。在野生型和Jα18−/−同基因淋巴瘤体内模型中，iNKT细胞恢复抗原特异性T细胞免疫的能力与髓系来源的抑制细胞(MDSCs)相似。因此，刺激iNKT细胞活性有可能作为一种针对AML的免疫疗法，或作为辅助手段来促进血液病或实体癌的抗原特异性T细胞免疫疗法。网上版载有补充材料，可在10.1007/s00262-022-03268-4查阅。
Acute myeloid leukaemia (AML) creates an immunosuppressive environment to conventional T cells through Arginase 2 (ARG2)-induced arginine depletion. We identify that AML blasts release the acute phase protein serum amyloid A (SAA), which acts in an autocrine manner to upregulate ARG2 expression and activity, and promote AML blast viability. Following in vitro cross-talk invariant natural killer T (iNKT) cells become activated, upregulate mitochondrial capacity, and release IFN-γ. iNKT retain their ability to proliferate and be activated despite the low arginine AML environment, due to the upregulation of Large Neutral Amino Acid Transporter-1 (LAT-1) and Argininosuccinate Synthetase 1 (ASS)-dependent amino acid pathways, resulting in AML cell death. T cell proliferation is restored in vitro and in vivo. The capacity of iNKT cells to restore antigen-specific T cell immunity was similarly demonstrated against myeloid-derived suppressor cells (MDSCs) in wild-type and Jα18−/− syngeneic lymphoma-bearing models in vivo. Thus, stimulation of iNKT cell activity has the potential as an immunotherapy against AML or as an adjunct to boost antigen-specific T cell immunotherapies in haematological or solid cancers. The online version contains supplementary material available at 10.1007/s00262-022-03268-4.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
DOI：
10.4049/jimmunol.1100500
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ather JL;Ckless K;Martin R;Foley KL;Suratt BT;Boyson JE;Fitzgerald KA;Flavell RA;Eisenbarth SC;Poynter ME
通讯作者：
Poynter ME
影响因子：
20.3
作者：
Le Dieu, Rifca;Taussig, David C.;Gribben, John G.
通讯作者：
Gribben, John G.
影响因子：
8.8
作者：
Carey A;Edwards DK 5th;Eide CA;Newell L;Traer E;Medeiros BC;Pollyea DA;Deininger MW;Collins RH;Tyner JW;Druker BJ;Bagby GC;McWeeney SK;Agarwal A
通讯作者：
Agarwal A