Abstract:
:The tumor microenvironment restrains conventional T cell (Tconv) activation while facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the tumor milieu relies on supplemental energetic routes involving lipid metabolism. In murine models, tumor-infiltrating Tregs displayed intracellular lipid accumulation, which was attributable to an increased rate of fatty acid (FA) synthesis. Since the relative advantage in glucose uptake may fuel FA synthesis in intratumoral Tregs, we demonstrated that both glycolytic and oxidative metabolism contribute to Tregs' expansion. We corroborated our data in human tumors showing that Tregs displayed a gene signature oriented toward glycolysis and lipid synthesis. Our data support a model in which signals from the tumor microenvironment induce a circuitry of glycolysis, FA synthesis, and oxidation that confers a preferential proliferative advantage to Tregs, whose targeting might represent a strategy for cancer treatment.
journal_name
Proc Natl Acad Sci U S Aauthors
Pacella I,Procaccini C,Focaccetti C,Miacci S,Timperi E,Faicchia D,Severa M,Rizzo F,Coccia EM,Bonacina F,Mitro N,Norata GD,Rossetti G,Ranzani V,Pagani M,Giorda E,Wei Y,Matarese G,Barnaba V,Piconese Sdoi
10.1073/pnas.1720113115subject
Has Abstractpub_date
2018-07-10 00:00:00pages
E6546-E6555issue
28eissn
0027-8424issn
1091-6490pii
1720113115journal_volume
115pub_type
杂志文章abstract::Ecological character displacement describes a pattern where morphological differences between sympatric species are enhanced through interspecific competition. Although widely considered a pervasive force in evolutionary ecology, few clear-cut examples have been documented. Here we report a case of ecological characte...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.8.4106
更新日期:2000-04-11 00:00:00
abstract::Reported effects of anti-CD154 treatment on autoimmunity, alloreactivity, and inflammatory events mediated by macrophages and endothelial cells indicated that it might be an ideal agent for the prevention of intrahepatic islet allograft failure. This hypothesis was tested in MHC-mismatched rhesus monkeys. Transplantat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.14.8132
更新日期:1999-07-06 00:00:00
abstract::Clear-cut inherited Mendelian traits, such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, account for <4% of colorectal cancers. Another 20% of all colorectal cancers are thought to occur in individuals with a significant inherited multifactorial susceptibility to colorectal cancer tha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407187101
更新日期:2004-11-09 00:00:00
abstract::The RAD52 epistasis group genes are involved in homologous DNA recombination, and their primary structures are conserved from yeast to humans. Although biochemical studies have suggested that the fundamental mechanism of homologous DNA recombination is conserved from yeast to mammals, recent studies of vertebrate cell...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.111006398
更新日期:2001-07-17 00:00:00
abstract::This paper is about an algorithm, FlexTree, for general supervised learning. It extends the binary tree-structured approach (Classification and Regression Trees, CART) although it differs greatly in its selection and combination of predictors. It is particularly applicable to assessing interactions: gene by gene and g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0403794101
更新日期:2004-07-20 00:00:00
abstract::The long-lived ethylene, cyclohexene, and norbornenemercurinium ions prepared in superacidic, low-nucleophilic media have been studied by (13)C and (199)Hg NMR spectroscopy. The norbornenemercurinium ion shows temperature-dependent (13)C and (199)Hg NMR spectra, consistent with equilibration via rapid hydride and Wagn...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.9.5036
更新日期:1980-09-01 00:00:00
abstract::The recognition of carrier proteins by multiple catalytic partners occurs in every cycle of chain elongation in the biosynthesis of fatty acids and of the pharmacologically important polyketide and nonribosomal peptide natural products. To dissect the features of carrier proteins that determine specific recognition at...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705122104
更新日期:2007-07-10 00:00:00
abstract::The linear ubiquitin assembly complex (LUBAC) comprises 3 components: HOIP, HOIL-1, and Sharpin, of which HOIP and HOIL-1 are both members of the RBR subfamily of E3 ubiquitin ligases. HOIP catalyses the formation of Met1-linked ubiquitin oligomers (also called linear ubiquitin), but the function of the E3 ligase acti...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1905873116
更新日期:2019-07-02 00:00:00
abstract::Rickettsiae are responsible for some of the most devastating human infections. A high infectivity and severe illness after inhalation make some rickettsiae bioterrorism threats. We report that deletion of the exchange protein directly activated by cAMP (Epac) gene, Epac1, in mice protects them from an ordinarily letha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1314400110
更新日期:2013-11-26 00:00:00
abstract::The CuAAC reaction (click chemistry) has been used in conjunction with solid-phase synthesis to produce catalytically active hairpin ribozymes around 100 nucleotides in length. Cross-strand ligation through neighboring nucleobases was successful in covalently linking presynthesized RNA strands with high efficiency (tr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1006447107
更新日期:2010-08-31 00:00:00
abstract::The 16S rRNA genes of Pyrobaculum aerophilum and Pyrobaculum islandicum were amplified by the polymerase chain reaction, and the resulting products were sequenced directly. The two organisms are closely related by this measure (over 98% similar). However, they differ in that the (lone) 16S rRNA gene of Pyrobaculum aer...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.6.2547
更新日期:1993-03-15 00:00:00
abstract::FK506-binding protein 52 (FKBP52), which binds FK506 and possesses peptidylprolyl isomerase activity, is an important immunophilin involved in the heterocomplex of steroid receptors with heat-shock protein 90. Here we report the crystal structures of two overlapped fragments [N(1-260) and C(145-459)] of FKBP52 and the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0305969101
更新日期:2004-06-01 00:00:00
abstract::The properties of the virus synthesized by each of three morphologically different cell lines originating from DBA/2J fetal liver cells transformed by the anemic strain of Friend leukemia virus in vitro were analyzed. The cells of line G-1 are malignant in syngeneic DBA/2 mice, grow in suspension, and are erythroid in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.10.5769
更新日期:1980-10-01 00:00:00
abstract::A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alt...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.15.5419
更新日期:1987-08-01 00:00:00
abstract::Up to half of all transcription termination events in bacteria rely on the RNA-dependent helicase Rho. However, the nucleic acid sequences that promote Rho-dependent termination remain poorly characterized. Defining the molecular determinants that confer Rho-dependent termination is especially important for understand...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1319193111
更新日期:2014-05-13 00:00:00
abstract::Atherosclerosis is a complex disease resulting from the interaction of multiple genes. We have used the Ldlr knockout mouse model in an interspecific genetic cross to map atherosclerosis susceptibility loci. A total of 174 (MOLF/Ei x B6.129S7-Ldlr(tm1Her)) x C57BL/6J-Ldlr(tm1Her) backcross mice, homozygous for the Ldl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.141239098
更新日期:2001-07-03 00:00:00
abstract::Wnt/beta-catenin signaling inhibits adipogenesis. Genome-wide profiling studies have revealed the enrichment of histone H3K27 methyltransferase Ezh2 on Wnt genes. However, the functional significance of such a direct link between the two types of developmental regulators in mammalian cells, and the role of Ezh2 in adi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1000031107
更新日期:2010-04-20 00:00:00
abstract::Murine mammary tumor virus (MMTV) expression is analyzed in a T-lymphoid cell line (T1M1) sensitive to the killing effect of glucocorticoids and in two of its variants, one resistant (T1M1r) and one supersensitive (T1M1ss) to glucocorticoid-induced lymphocytolysis. In the T1M1 line, MMTV is expressed and induced appro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.1.110
更新日期:1983-01-01 00:00:00
abstract::The Bacillus subtilis phage SP01, whose DNA contains 5-hydroxymethyluracil (hmUra) in place of thymine, codes for an abundant, small, basic protein called TF1. TF1 binds preferentially to hydroxymethyluracil-containing DNA and thereby selectively inhibits transcription of such DNA in vitro. The gene for TF1 has been s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.22.7031
更新日期:1984-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.4.1147
更新日期:1995-02-14 00:00:00
abstract::A heterogeneous RNA fraction with properties resembling those of messenger RNA was identified in mammalian mitochondria. Synthesis of contaminating RNA of nuclear origin was suppressed by treatment with camptothecin. Labeling of the messenger-like RNA is completely inhibited by ethidium bromide, a specific inhibitor o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.2.350
更新日期:1973-02-01 00:00:00
abstract::The elevation of Ca2+ levels in the cytoplasm inactivates inward-rectifying K+ channels that play a central role in regulating the apertures of stomatal pores in higher plants. However, the mechanism for the Ca(2+)-mediated inhibition of K(+)-channel function is unknown. Using patch-clamp techniques, we show that cycl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.6.2202
更新日期:1993-03-15 00:00:00
abstract::An efficient technique has been developed for performing in vivo site-directed mutagenesis in Drosophila melanogaster. This procedure involves directed repair of P-element-induced DNA lesions after injection of a modified DNA sequence into early embryos. An oligonucleotide of 50 base pairs, whose sequence spans the P-...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.5.1735
更新日期:1992-03-01 00:00:00
abstract::In the T-cell somatic mutant J.CaM1, the T-cell antigen receptor complex is poorly coupled to the inositolphospholipid second messenger system; some antibodies against the invariant CD3 subunit of the receptor retain their agonist function in J.CaM1. Here we show by a combination of complementation assays that the mut...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.22.8613
更新日期:1988-11-01 00:00:00
abstract::The cdc25 phosphatases play key roles in cell cycle progression by activating cyclin-dependent kinases. Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.17.7892
更新日期:1995-08-15 00:00:00
abstract::Here the first reproductive sterility system for the tephritid fruit fly pest, Anastrepha suspensa, is presented, based on lethality primarily limited to embryos heterozygous for a conditional lethal transgene combination. This tetracycline (Tet)-suppressible system uses a driver construct having the promoter from the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1203352109
更新日期:2012-06-12 00:00:00
abstract::Although potassium channels play a variety of roles in shaping the electrical properties of neurons, little is known about how these channels are constituted in neurons. To examine the assembly and physiological function of A-type K+ channels in mature differentiated neurons, we have developed a highly efficient gene ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.3.1133
更新日期:1992-02-01 00:00:00
abstract::One of the serious limitations of tokamaks as reactors is the occurrence of disruptions. Stellarators designed by advanced computational methods provide an attractive alternative for a major experiment in magnetic fusion research. Configurations with approximate two-dimensional magnetic symmetry have been found with h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.3.972
更新日期:2000-02-01 00:00:00
abstract::We examined the distributions of short tandemly repeated DNAs (microsatellites) in nine complete microbial genomes (Saccharomyces cerevisiae, Archaeoglobus fulgidus, Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Methanococcus jannaschii, Mycoplasma pneumoniae, M. genitalium, and Synechocystis PCC6803....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.4.1647
更新日期:1998-02-17 00:00:00
abstract::Inbred Lewis (LEW/N) female rats develop an arthritis in response to group A streptococcal cell wall peptidoglycan polysaccharide (SCW), which mimics human rheumatoid arthritis. Histocompatible Fischer (F344/N) rats do not develop arthritis in response to the same SCW stimulus. To evaluate this difference in inflammat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.7.2374
更新日期:1989-04-01 00:00:00