至今,GenScript的服务及产品已被Cell, Nature, Science, PNAS等1300多家生物医药类杂志引用近万次,处于行业领先水平。NIH、哈佛、耶鲁、斯坦福、普林斯顿、杜克大学等约400家全球著名机构使用GenScript的基因合成、多肽服务、抗体服务和蛋白服务等成功地发表科研成果,再次证明GenScript 有能力帮助业内科学家Make research easy.

RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer.

Cancer Cell. 2018; 
Wang W, Marinis JM, Beal AM, Savadkar S, Wu Y, Khan M, Taunk PS, Wu N, Su W, Wu J, Ahsan A, Kurz E, Chen T, Yaboh I, Li F, Gutierrez J, Diskin B, Hundeyin M, Reilly M, Lich JD, Harris PA, Mahajan MK, Thorpe JH, Nassau P, Mosley JE, Leinwand J, Kochen Rossi JA, Mishra A, Aykut B, Glacken M, Ochi A, Verma N, Kim JI, Vasudevaraja V, Adeegbe D, Almonte C, Bagdatlioglu E, Cohen DJ, Wong KK, Bertin J, Miller G.
Products/Services Used Details Operation
Recombinant Antibody Services Continued REAGENT or RESOURCE SOURCE IDENTIFIER QVD-Oph Millipore Sigma 551476 Recombinant human TNFa R&D systems 210-TA-100 FLAG-RIPK1 1-294 (C34A C127A C233A C240A) Genscript N/A fluorescently-labeled ligand (14-(2-{[3-({2-{[4-(cyanomethyl)phenyl]amino}- 6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-4-pyrimidinyl}amino) propyl] amino}-2-oxoethyl)-16,16,18,18-tetramethyl-6,7,7a,8a,9,10,16,18- octahydrobenzo [2’,3’]indolizino[8’,7’:5 ,6 ]pyrano [3 ,2 :3,4]pyrido[1,2-a] indol-5-ium-2-sulfonate) 0 0 0 0 GSK N/A Critical Commercial Assays MILLIPLEX Human Cytokine 41-Plex kit MilliporeSigma Cat#: HCYTMAG-60K-PX41 Reaction Biology Kinase Assay Reaction Biology Corp Wild type kinase panel Cell Titre-Glo Luminescent Cell Viability Assay Promega G7573 Deposited Data X-ray crystalllography data, maps and structure coordinates: PDB This paper 6HHO https://www. Get A Quote

摘要

Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 (RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCIIhiTNFα+IFNγ+ immunogenic phenotype in a STAT1-dependent manner. RIP1 inhibition in TAMs resulted in cytotoxic T cell activation and T helper cell differentiation toward a mixed Th1/Th17 phenotype, leading to tumor immunity in mice and in organotypic models of human PDA. Targeting RIP1 synerg... More

关键词

Pancreatic cancer; inflammation; macrophage polarization; tumor immunity