| First Author | Xia H | Year | 2017 |
| Journal | Sci Immunol | Volume | 2 |
| Issue | 17 | PubMed ID | 29150439 |
| Mgi Jnum | J:261261 | Mgi Id | MGI:6141455 |
| Doi | 10.1126/sciimmunol.aan4631 | Citation | Xia H, et al. (2017) Suppression of FIP200 and autophagy by tumor-derived lactate promotes naive T cell apoptosis and affects tumor immunity. Sci Immunol 2(17) |
| abstractText | Naive T cells are poorly studied in cancer patients. We report that naive T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bak1 Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity. Tumor-derived lactate translationally inhibits FIP200 expression by down-regulating the nicotinamide adenine dinucleotide level while potentially up-regulating the inhibitory effect of adenylate-uridylate-rich elements within the 3'' untranslated region of Fip200 mRNA. Thus, tumors metabolically target naive T cells to evade immunity. |
