2025
Bile acid synthesis impedes tumor-specific T cell responses during liver cancer
Varanasi S, Chen D, Liu Y, Johnson M, Miller C, Ganguly S, Lande K, LaPorta M, Hoffmann F, Mann T, Teneche M, Casillas E, Mangalhara K, Mathew V, Sun M, Jensen I, Farsakoglu Y, Chen T, Parisi B, Deota S, Havas A, Lee J, Chung H, Schietinger A, Panda S, Williams A, Farber D, Dhar D, Adams P, Feng G, Shadel G, Sundrud M, Kaech S. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science 2025, 387: 192-201. PMID: 39787217, PMCID: PMC12166762, DOI: 10.1126/science.adl4100.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsBile Acids and SaltsCarcinoma, HepatocellularCD8-Positive T-LymphocytesCell Line, TumorEndoplasmic Reticulum StressHepatocytesHumansImmune Checkpoint InhibitorsImmunotherapyLithocholic AcidLiver NeoplasmsMiceOxidative StressProgrammed Cell Death 1 ReceptorTumor MicroenvironmentUrsodeoxycholic AcidConceptsTumor-specific T-cell responsesT cell responsesAnti-programmed cell death protein 1Ursodeoxycholic acidCell death protein 1CD8<sup>+</sup> T cellsBile acidsFeatures of human hepatocellular carcinomaImprove tumor immunotherapyInfluence antitumor immunityT cell functionReduced tumor growthBA synthesisLiver cancer modelCancer model systemsHuman hepatocellular carcinomaLandscape of cancerAntitumor immunityTumor immunotherapySecondary bile acidsOrgan-specific metabolitesEndoplasmic reticulum stressT cellsCancer modelsDietary intake
2024
Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling.
Xu Z, Kuhlmann-Hogan A, Xu S, Tseng H, Chen D, Tan S, Sun M, Tripple V, Bosenberg M, Miller-Jensen K, Kaech S. Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling. Cancer Research 2024, 85: 462-476. PMID: 39546763, PMCID: PMC11788022, DOI: 10.1158/0008-5472.can-23-4027.Peer-Reviewed Original ResearchTumor-associated macrophagesIFN-ITumor microenvironmentTumor growthHeterogeneous population of myeloid cellsPharmacological inhibition of CD36Population of myeloid cellsTumor cell quiescenceAnti-tumor immunityDelayed tumor growthTumor inflammatory microenvironmentElevated type I interferonReduced tumor growthMyeloid-specific deletionDeletion of CD36Type I Interferon SignalingInhibition of CD36Promote cancer progressionI interferon signalingIFN-I responseIFN-I signalingType I interferonScavenger receptor CD36TAM functionNatural suppressorPerivascular NOTCH3+ Stem Cells Drive Meningioma Tumorigenesis and Resistance to Radiotherapy.
Choudhury A, Cady M, Lucas C, Najem H, Phillips J, Palikuqi B, Zakimi N, Joseph T, Birrueta J, Chen W, Oberheim Bush N, Hervey-Jumper S, Klein O, Toedebusch C, Horbinski C, Magill S, Bhaduri A, Perry A, Dickinson P, Heimberger A, Ashworth A, Crouch E, Raleigh D. Perivascular NOTCH3+ Stem Cells Drive Meningioma Tumorigenesis and Resistance to Radiotherapy. Cancer Discovery 2024, 14: 1823-1837. PMID: 38742767, PMCID: PMC11452293, DOI: 10.1158/2159-8290.cd-23-1459.Peer-Reviewed Original ResearchConceptsResistance to radiotherapyMeningioma tumorigenesisSystemic therapyTreating meningiomasStem cellsGenetically engineered mouse modelsTumor-initiating capacityHigh-grade meningiomasReduced tumor growthPrimary intracranial tumorsMeningioma growthImproved survivalIntracranial tumorsRadiotherapyTherapeutic vulnerabilitiesTumor growthMeningiomasMouse modelSingle-cell transcriptomicsLineage tracingNotch3TumorigenesisCell proliferationReduced survivalCell typesTumor expressed BCAM impedes anti-tumor T cell immunity and can be targeted therapeutically
Flies D, Tian L, O'Neill R, Fitzgerald D, Sharee S, Shaik J, Bosiacki J, Paucarmayta A, Prajapati K, Langermann S, Mrass P. Tumor expressed BCAM impedes anti-tumor T cell immunity and can be targeted therapeutically. The Journal Of Immunology 2024, 212: 0517_5466-0517_5466. DOI: 10.4049/jimmunol.212.supp.0517.5466.Peer-Reviewed Original ResearchAnti-tumor immunityT cell immunityCytotoxic T cellsTumor microenvironmentT cellsTumor growthAnti-tumor T cell immunityT cell anti-tumor immunityExclusion of T cellsIncreased T-cell infiltrationRegulating T cell immunityHuman T cell functionT cell infiltrationInhibitor of T cell proliferationT cell suppressionHuman tumors in vitroT cell functionReduced tumor growthT cell proliferationDecreased tumor growthTumors in vitroTumor growth in vivoCancer escapeCheckpoint inhibitorsGrowth in vivoThe IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer
Amara C, Kami Reddy K, Yuntao Y, Chan Y, Piyarathna D, Dobrolecki L, Shih D, Shi Z, Xu J, Huang S, Ellis M, Apolo A, Ballester L, Gao J, Hansel D, Lotan Y, Hodges H, Lerner S, Creighton C, Sreekumar A, Zheng W, Msaouel P, Kavuri S, Putluri N. The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer. Nature Communications 2024, 15: 1373. PMID: 38355560, PMCID: PMC10867091, DOI: 10.1038/s41467-024-45132-2.Peer-Reviewed Original ResearchConceptsSignaling AxisSMARCB1-deficient tumorsSMARCB1 deficiencyBladder cancerChromatin accessibilitySTAT3 inhibitorTumor growthSMARCB1 lossPatient-derived xenograft modelsCell line-derived xenograftsTherapeutic vulnerabilitiesTarget pathwaysReduced tumor growthIncreased tumor growthCell linesIn vivo modelsSTAT3Gene signatureSMARCB1TTI-101Solid tumorsXenograft modelClinical evaluationDisease progressionTumor
2023
Everolimus combined with PD-1 blockade inhibits progression of triple-negative breast cancer
Li G, Hu J, Cho C, Cui J, Li A, Ren P, Zhou J, Wei W, Zhang T, Liu X, Liu W. Everolimus combined with PD-1 blockade inhibits progression of triple-negative breast cancer. Cellular Signalling 2023, 109: 110729. PMID: 37257766, DOI: 10.1016/j.cellsig.2023.110729.Peer-Reviewed Original ResearchConceptsT cell tumor infiltrationTriple-negative breast cancerCD8+ T cell tumor infiltrationBreast cancerTumor infiltrationLack of target receptorsAnti-PD-1 antibodyAggressive subtype of breast cancerModels of triple-negative breast cancerSubtypes of breast cancerPD-L1 expressionEstrogen-positive breast cancerMTOR inhibitor everolimusPositive breast cancerProgression of triple-negative breast cancerReduced tumor growthAvailable treatment optionsCombination treatment strategiesPromote cancer cell survivalTreatment of estrogen-positive breast cancerAttenuate tumor progressionNonspecific cytotoxic agentsCancer cell survivalVascular endothelial cellsPotential therapeutic strategyA Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies
Chee C, Ooi M, Lee S, Sundar R, Heong V, Yong W, Ng C, Wong A, Lim J, Tan D, Soo R, Tan J, Yang S, Thura M, Al-Aidaroos A, Chng W, Zeng Q, Goh B. A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies. Targeted Oncology 2023, 18: 391-402. PMID: 37060431, PMCID: PMC10192144, DOI: 10.1007/s11523-023-00962-w.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAdvanced solid tumorsFirst-in-human studyEuropean Leukemia NetworkSolid tumorsHematologic malignanciesTreatment-emergent adverse eventsHuman antibodiesDose-escalation cohortsDose-limiting toxicityGrade 2 vomitingPRL-3Refractory solid tumorsResponse Evaluation CriteriaSolid tumor patientsDose-expansion cohortReduced tumor growthFirst-in-humanPhase IStable diseaseStoma outputEvaluation CriteriaMyeloid leukemiaPharmacodynamic relationshipsAdverse events
2021
Neoadjuvant Cabozantinib in an Unresectable Locally Advanced Renal Cell Carcinoma Patient Leads to Downsizing of Tumor Enabling Surgical Resection: A Case Report
Bilen M, Jiang J, Jansen C, Brown J, Harik L, Sekhar A, Kissick H, Maithel S, Kucuk O, Carthon B, Master V. Neoadjuvant Cabozantinib in an Unresectable Locally Advanced Renal Cell Carcinoma Patient Leads to Downsizing of Tumor Enabling Surgical Resection: A Case Report. Frontiers In Oncology 2021, 10: 622134. PMID: 33598435, PMCID: PMC7882722, DOI: 10.3389/fonc.2020.622134.Peer-Reviewed Original ResearchRenal cell carcinomaMetastatic renal cell carcinomaMagnetic resonance imagingSurgical resectionNeoadjuvant settingCell carcinomaAdvanced renal cell carcinoma patientsLocally advanced renal cell carcinomaLeft renal cell carcinomaUnresectable renal cell carcinomaAdvanced renal cell carcinomaInvasion of adjacent structuresRenal cell carcinoma patientsNeoadjuvant systemic therapySecond-line settingSplenic flexure of colonTumor size reductionCell carcinoma patientsTail of pancreasReduced tumor growthAdjacent structuresTyrosine kinase c-MetCABOSUN trialPosterior abdominal wallTumor diameter
2017
The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression
Pan W, Zhu S, Qu K, Meeth K, Cheng J, He K, Ma H, Liao Y, Wen X, Roden C, Tobiasova Z, Wei Z, Zhao J, Liu J, Zheng J, Guo B, Khan SA, Bosenberg M, Flavell RA, Lu J. The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression. Immunity 2017, 47: 284-297.e5. PMID: 28813659, PMCID: PMC5710009, DOI: 10.1016/j.immuni.2017.07.020.Peer-Reviewed Original ResearchConceptsImmunosuppressive functionMyeloid cellsIntratumoral myeloid cellsNon-hematologic malignanciesMyeloid-specific deletionTumor-associated macrophagesReduced tumor growthTumor-promoting functionsProinflammatory onesMyD88 pathwayMelanoma patientsCell depletionEffector TRole of TET2Methylcytosine dioxygenase TET2Mouse modelIL-1RMelanoma growthTherapeutic targetTumor growthTET2 expressionMelanoma progressionHematopoietic malignanciesMalignancyTET2
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