Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchMeSH KeywordsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansLung NeoplasmsSignal TransductionConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutationsParaoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport
Nagarajan A, Dogra SK, Sun L, Gandotra N, Ho T, Cai G, Cline G, Kumar P, Cowles RA, Wajapeyee N. Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport. Molecular Cell 2017, 67: 685-701.e6. PMID: 28803777, PMCID: PMC5567863, DOI: 10.1016/j.molcel.2017.07.014.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntineoplastic AgentsApoptosis Regulatory ProteinsAryldialkylphosphataseCarcinoma, Pancreatic DuctalCell Line, TumorCell MovementCell ProliferationEnergy MetabolismFemaleForkhead Box Protein O3Gene Expression Regulation, NeoplasticGlucoseGlucose Transporter Type 1HumansLiver NeoplasmsLung NeoplasmsMaleMice, NudeMutationPancreatic NeoplasmsProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)RNA InterferenceSignal TransductionTime FactorsTranscription, GeneticTransfectionTumor BurdenTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsPDAC tumor growthGlucose transportCellular starvation responsesParaoxonase 2Glutamine metabolism pathwayNew metabolic regulatorPDAC tumor samplesShort hairpin RNATumor growthStarvation responseMetabolic genesTranscriptional targetsProtein kinaseTractable pathwayPancreatic cancer growthGenetic activationMetabolism pathwaysHairpin RNAMetabolic regulatorNew modulatorsHuman cancersPancreatic ductal adenocarcinomaMetabolic deregulationAMPKCancer growth