| First Author | Ding S | Year | 2023 |
| Journal | Immunology | Volume | 170 |
| Issue | 1 | Pages | 28-46 |
| PubMed ID | 37094816 | Mgi Jnum | J:361473 |
| Mgi Id | MGI:7857031 | Doi | 10.1111/imm.13650 |
| Citation | Ding S, et al. (2023) Deficiency of angiopoietin-like 4 enhances CD8(+) T cell bioactivity via metabolic reprogramming for impairing tumour progression. Immunology 170(1):28-46 |
| abstractText | Angiopoietin-like 4 (ANGPTL4) is a secreted metabolism-modulating glycoprotein involved in the progression of tumours, cardiovascular diseases, metabolic syndrome and infectious diseases. In this study, more CD8(+) T cells were activated to be effector T cells in ANGPTL4(-/-) mice. Impaired growth of tumours implanted in 3LL, B16BL6 or MC38 cells and reduced metastasis by B16F10 cells were observed in ANGPTL4(-/-) mice. Bone marrow (BM) transplantation experiments displayed that deficiency of ANGPTL4 in either host or BM cells promoted CD8(+) T cell activation. However, ANGPTL4 deficiency in CD8(+) T cells themselves showed more efficient anti-tumour activities. Recombinant ANGPTL4 protein promoted tumour growth in vivo with the less CD8(+) T cell infiltration and it directly downregulated CD8(+) T cell activation ex vivo. Transcriptome sequencing and metabolism analysis identified that ANGPTL4(-/-) CD8(+) T cells increased glycolysis and decreased oxidative phosphorylation, which was dependent on the PKCzeta-LKB1-AMPK-mTOR signalling axis. Reverse correlation of elevated ANGPTL4 levels in sera and tumour tissues with activated CD8(+) T cells in the peripheral blood was displayed in patients with colorectal cancer. These results demonstrated that ANGPTL4 decreased immune surveillance in tumour progression by playing an immune-modulatory role on CD8(+) T cells via metabolic reprogramming. Efficient blockade of ANGPTL4 expression in tumour patients would generate an effective anti-tumour effect mediated by CD8(+) T cells. |
