期刊
CANCER RESEARCH
卷 76, 期 21, 页码 6193-6204出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-15-3502
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资金
- Cancer Research UK [17722, 11331, 23969] Funding Source: researchfish
- Medical Research Council [MC_UU_12010/1, G1000800e, 1239050, G1000800] Funding Source: researchfish
- Cancer Research UK [11331, A11331, C399/A2291] Funding Source: Medline
- Medical Research Council [MC_UU_12010/1, G1000800] Funding Source: Medline
- MRC [MC_UU_12010/1, G1000800] Funding Source: UKRI
Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated isoforms, which in turn enhanced tryptophan and glutamine uptake. Importantly, SLC1A5 failed to be upregulated in resting human T cells kept under low tryptophan conditions but was enhanced upon cognate antigen T-cell receptor engagement. Our results highlight key differences in the ability of tumor and T cells to adapt to tryptophan starvation and provide important insights into the poor prognosis of tumors coexpressing IDO and SLC1A5.
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