2019
Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer
Sivaram N, McLaughlin PA, Han HV, Petrenko O, Jiang YP, Ballou LM, Pham K, Liu C, van der Velden A, Lin RZ. Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. Journal Of Clinical Investigation 2019, 129: 3264-3276. PMID: 31112530, PMCID: PMC6668699, DOI: 10.1172/jci123540.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCell Line, TumorClass I Phosphatidylinositol 3-KinasesHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMiceMice, KnockoutMice, SCIDNeoplasms, ExperimentalPancreatic NeoplasmsProto-Oncogene Proteins c-aktSignal TransductionT-LymphocytesXenograft Model Antitumor AssaysConceptsPancreatic cancerT cellsT cell-deficient miceTumor-infiltrating T cellsAntigen-experienced T cellsCell-deficient miceFavorable patient outcomesOrthotopic implantation modelComplete tumor regressionMost pancreatic cancersT cell surveillanceT cell recognitionPancreatic cancer cellsMHC class IAvailable immunotherapiesAdoptive transferEffective immunotherapyTumor immunogenicityTumor regressionPancreatic tumorsPatient outcomesHost miceImmunodeficient miceCell surveillanceTumors
2017
Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to Promote a Tumor-Tolerant Immune Microenvironment
Delitto D, Delitto AE, DiVita BB, Pham K, Han S, Hartlage ER, Newby BN, Gerber MH, Behrns KE, Moldawer LL, Thomas RM, George TJ, Brusko TM, Mathews CE, Liu C, Trevino JG, Hughes SJ, Wallet SM. Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to Promote a Tumor-Tolerant Immune Microenvironment. Cancer Research 2017, 77: 672-683. PMID: 27864347, PMCID: PMC5290036, DOI: 10.1158/0008-5472.can-16-1765.Peer-Reviewed Original ResearchConceptsTumor-associated stromaPancreatic cancerTumor microenvironmentT cell-mediated cytotoxicityCancer cell-conditioned mediumImmunosuppressive tumor microenvironmentT cell proliferationCell-conditioned mediumHuman cell culture modelsTh1 ratioProtective immunityCancer differsHealthy controlsMemory Th17Pancreatic lysatesCell culture modelPrimary human cell culture modelsRobust secretionCancer cellsCD8TA responsesPatientsImmunomodulatory characterCancerCulture model
2015
Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer
Delitto D, Perez C, Han S, Gonzalo DH, Pham K, Knowlton AE, Graves CL, Behrns KE, Moldawer LL, Thomas RM, Liu C, George TJ, Trevino JG, Wallet SM, Hughes SJ. Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer. Cancer Immunology, Immunotherapy 2015, 64: 1553-1563. PMID: 26423423, PMCID: PMC5129167, DOI: 10.1007/s00262-015-1760-y.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityCell Line, TumorChemokine CXCL10DeoxycytidineDrug Resistance, NeoplasmEnzyme-Linked Immunosorbent AssayFlow CytometryGemcitabineGene Expression Regulation, NeoplasticHLA AntigensHumansInterferon-gammaInterferonsPancreatic NeoplasmsReceptors, CXCR3Tumor Cells, CulturedTumor MicroenvironmentConceptsPC cell linesPancreatic cancerAntitumor immunityPoor survivalPC microenvironmentHuman leukocyte antigen (HLA) class IMinimal inflammatory cell infiltrationEffective antitumor immunityImmune checkpoint ligandsUpregulation of PDL1Inflammatory cell infiltrationAntigen class IHuman pancreatic cancerAbsence of CD80Tumor-associated stromaCell linesCancer epithelial cellsCheckpoint ligandsCXCL10 concentrationsCell typesIFNγ responsesIndependent predictorsCD86 expressionChronic pancreatitisCell infiltration