2022
Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells.
McBrearty N, Cho C, Chen J, Zahedi F, Peck A, Radaelli E, Assenmacher C, Pavlak C, Devine A, Yu P, Lu Z, Zhang H, Li J, Pitarresi J, Astsaturov I, Cukierman E, Rustgi A, Stanger B, Rui H, Fuchs S. Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells. Molecular Cancer Research 2022, 21: 228-239. PMID: 36378658, PMCID: PMC9992122, DOI: 10.1158/1541-7786.mcr-22-0602.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPancreatic cancer cellsPDAC cellsCH25H expressionTumor growthT cell tumor infiltrationMouse PDAC cellsImmune checkpoint inhibitorsCancer cellsDownregulation of MHCPancreatic intraepithelial neoplasiaImmune-competent hostsHuman pancreatic cancerPotential translational importanceAccumulation of cholesterolCheckpoint inhibitorsIntraepithelial neoplasiaPoor prognosisTumor infiltrationPancreatic cancerDuctal adenocarcinomaTherapeutic approachesCH25HTumor progressionCholesterol deficitInduction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities
Lu Z, Bae E, Verginadis I, Zhang H, Cho C, McBrearty N, George S, Diehl J, Koumenis C, Bradley L, Fuchs S. Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities. Cancer Immunology, Immunotherapy 2022, 72: 815-826. PMID: 36063172, PMCID: PMC10317204, DOI: 10.1007/s00262-022-03286-2.Peer-Reviewed Original ResearchConceptsActivity of CD8Tumor-derived factorsT cellsTumor microenvironmentTranscription factor 4Anti-tumor immunityImmune suppressive factorsFactor 4Anti-tumor activityFunction of ATF4Anti-cancer therapyIntratumoral CD8Cytotoxic CD8Immune therapyTherapeutic regimensAntigenic stimulationCD8Suppressive factorsT lymphocytesMouse modelImpaired activationWild-type counterpartsSelective ablationTherapyInduction of ATF4Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy
Hu L, Chen L, Xiao Z, Zheng X, Chen Y, Xian N, Cho C, Luo L, Huang G, Chen L. Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy. JCI Insight 2022, 7: e148247. PMID: 34905507, PMCID: PMC8855794, DOI: 10.1172/jci.insight.148247.Peer-Reviewed Original ResearchConceptsPD-1HT cellsAdoptive immunotherapyT cell-mediated immune responsesT-cell adoptive immunotherapyAdoptive T-cell therapyCell-mediated immune responsesTumor-infiltrating CD8Antitumor activityT-cell therapySyngeneic mouse tumorsCAR T cellsDeath-1 homologExperimental tumor modelsAdoptive transferActivated CD8Coinhibitory moleculesCytokine productionDeficient miceImmune responseHuman xenograftsCD8Tumor microenvironmentTumor modelMouse tumors
2021
Regulation of intercellular biomolecule transfer–driven tumor angiogenesis and responses to anticancer therapies
Lu Z, Ortiz A, Verginadis I, Peck A, Zahedi F, Cho C, Yu P, DeRita R, Zhang H, Kubanoff R, Sun Y, Yaspan A, Krespan E, Beiting D, Radaelli E, Ryeom S, Diehl J, Rui H, Koumenis C, Fuchs S. Regulation of intercellular biomolecule transfer–driven tumor angiogenesis and responses to anticancer therapies. Journal Of Clinical Investigation 2021, 131: e144225. PMID: 33998600, PMCID: PMC8121529, DOI: 10.1172/jci144225.Peer-Reviewed Original ResearchConceptsTumor growthEndothelial cellsMetastatic diseaseAnticancer therapyPoor disease outcomeColorectal cancerIntratumoral angiogenesisAngiostatic effectsDisease outcomeTherapeutic effectSide effectsOverall efficacyPharmacologic inhibitionTumor angiogenesisCH25HTherapyBenign cellsAngiogenesisDiseaseLow levelsCellsRegimensPatientsReserpineCancer
2020
Cancer-associated fibroblasts downregulate type I interferon receptor to stimulate intratumoral stromagenesis
Cho C, Mukherjee R, Peck AR, Sun Y, McBrearty N, Katlinski KV, Gui J, Govindaraju PK, Puré E, Rui H, Fuchs SY. Cancer-associated fibroblasts downregulate type I interferon receptor to stimulate intratumoral stromagenesis. Oncogene 2020, 39: 6129-6137. PMID: 32807917, PMCID: PMC7502515, DOI: 10.1038/s41388-020-01424-7.Peer-Reviewed Original ResearchConceptsCancer-associated fibroblastsFibroblast activation proteinType I interferon receptorTumor growthPancreatic ductal adenocarcinoma tumorsInterferon receptorKnockdown of Smad7Human colorectal cancerGrowth of tumorsSA miceColorectal cancerAdenocarcinoma tumorsSolid tumorsIFNAR1 downregulationGenetic ablationTumorsActivation proteinElevated levelsExtracellular matrixInverse correlationMiceStromagenesisIFNAR1IFNAR1 chainFAP levels
2019
An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
Ortiz A, Gui J, Zahedi F, Yu P, Cho C, Bhattacharya S, Carbone CJ, Yu Q, Katlinski KV, Katlinskaya YV, Handa S, Haas V, Volk SW, Brice AK, Wals K, Matheson NJ, Antrobus R, Ludwig S, Whiteside TL, Sander C, Tarhini AA, Kirkwood JM, Lehner PJ, Guo W, Rui H, Minn AJ, Koumenis C, Diehl JA, Fuchs SY. An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles. Cancer Cell 2019, 35: 33-45.e6. PMID: 30645975, PMCID: PMC6336114, DOI: 10.1016/j.ccell.2018.12.001.Peer-Reviewed Original ResearchConceptsTumor-derived extracellular vesiclesMelanoma lung metastasisPre-metastatic nicheLung metastasesAdjuvant melanoma therapyAnti-hypertensive drugsUse of reserpineExtracellular vesiclesType I interferon receptorMelanoma patientsPoor prognosisCH25HMelanoma therapyIFN receptorInterferon receptorMetastasisNormal cellsHealthy cellsReceptorsUptakeCellsPatientsPrognosisReserpineTherapy