2024
Spatially resolved tissue imaging to analyze the tumor immune microenvironment: beyond cell-type densities
Janeiro A, Wong E, Jiménez-Sánchez D, de Solorzano C, Lozano M, Teijeira A, Schalper K, Melero I, De Andrea C. Spatially resolved tissue imaging to analyze the tumor immune microenvironment: beyond cell-type densities. Journal For ImmunoTherapy Of Cancer 2024, 12: e008589. PMID: 38821717, PMCID: PMC11149121, DOI: 10.1136/jitc-2023-008589.Peer-Reviewed Original ResearchUp-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulatedVascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumor
2023
Neuroendocrine lineage commitment of small cell lung cancers can be leveraged into p53-independent non-cytotoxic therapy
Biswas S, Kang K, Ng K, Radivoyevitch T, Schalper K, Zhang H, Lindner D, Thomas A, MacPherson D, Gastman B, Schrump D, Wong K, Velcheti V, Saunthararajah Y. Neuroendocrine lineage commitment of small cell lung cancers can be leveraged into p53-independent non-cytotoxic therapy. Cell Reports 2023, 42: 113016. PMID: 37597186, PMCID: PMC10528072, DOI: 10.1016/j.celrep.2023.113016.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerNon-cytotoxic therapiesImmune checkpoint inhibitorsCell lung cancerDNA methyltransferase 1SCLC cellsCytotoxic chemotherapyLung cancerDisseminated small cell lung cancerRepression marksSurvival of miceLineage commitmentCheckpoint inhibitorsResistant therapiesMaster transcription factorMaturation arrestTherapyTranscription factorsClinical compoundsMethyltransferase 1DNMT1 knockdownChemotherapyLineage maturationTranslocation 2Neuroendocrine lineage
2016
Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming
Rodriguez-Ruiz ME, Rodriguez I, Garasa S, Barbes B, Solorzano JL, Perez-Gracia JL, Labiano S, Sanmamed MF, Azpilikueta A, Bolaños E, Sanchez-Paulete AR, Aznar MA, Rouzaut A, Schalper KA, Jure-Kunkel M, Melero I. Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming. Cancer Research 2016, 76: 5994-6005. PMID: 27550452, DOI: 10.1158/0008-5472.can-16-0549.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBasic-Leucine Zipper Transcription FactorsCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansLymphocytes, Tumor-InfiltratingMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalProgrammed Cell Death 1 ReceptorReceptor, Interferon alpha-betaRepressor ProteinsTumor MicroenvironmentTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsAnti-CD137 mAbsCD8 T cellsEffector T cellsT cellsTumor lesionsMyeloid-derived suppressor cellsSelective depletion experimentsType I IFN systemTumor-infiltrating lymphocytesCombination of radiotherapyField of irradiationImmunostimulatory mAbsImmunotherapy combinationsIntracellular IFNγProimmune effectsContralateral tumorsSuppressor cellsDendritic cellsClinical evidenceRadiotherapy strategiesIrradiation regimenAntitumor effectsClinical developmentTumor siteEx vivo
2015
Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2−/−IL2Rγnull Immunodeficient Mice
Sanmamed MF, Rodriguez I, Schalper KA, Oñate C, Azpilikueta A, Rodriguez-Ruiz ME, Morales-Kastresana A, Labiano S, Pérez-Gracia JL, Martín-Algarra S, Alfaro C, Mazzolini G, Sarno F, Hidalgo M, Korman AJ, Jure-Kunkel M, Melero I. Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2−/−IL2Rγnull Immunodeficient Mice. Cancer Research 2015, 75: 3466-3478. PMID: 26113085, DOI: 10.1158/0008-5472.can-14-3510.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalColorectal NeoplasmsDNA-Binding ProteinsGraft vs Host DiseaseHT29 CellsHumansInterleukin Receptor Common gamma SubunitLeukocytes, MononuclearLymphocyte ActivationMiceNivolumabProgrammed Cell Death 1 ReceptorT-LymphocytesTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsPeripheral blood mononuclear cellsT lymphocytesHuman T lymphocytesAllogeneic human peripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsT cell-mediated diseaseImmune checkpoint drugsImmunostimulatory monoclonal antibodiesCell-mediated diseaseRegulatory T lymphocytesHumanized murine modelBlood mononuclear cellsHumanized mouse modelPreclinical model systemsLymphocyte infiltrationTherapeutic regimenMononuclear cellsCell surface expressionCancer immunologyGastric carcinomaImmunodeficient miceMurine modelMouse modelSame patientTumor xenograftsSpironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of mineralocorticoid-induced hypertensive rats
Carreño JE, Verdugo FJ, Contreras F, Montellano FA, Veloso S, Schalper KA, Sandoval M, Villanueva S, Marusic E, Irarrazabal CE. Spironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of mineralocorticoid-induced hypertensive rats. Journal Of The Renin-Angiotensin-Aldosterone System 2015, 16: 1225-1231. PMID: 25997821, DOI: 10.1177/1470320315587193.Peer-Reviewed Original ResearchConceptsNHE-1 activityMineralocorticoid receptor activationEthyl isopropyl amilorideVascular contractilityHypertensive ratsReceptor activationMale Sprague-Dawley ratsUninephrectomized male Sprague-Dawley ratsChronic DOCA treatmentDiastolic blood pressureAortic wall thicknessWeeks of treatmentVascular smooth muscle cellsProtein levelsSprague-Dawley ratsSmooth muscle cellsNHE-1 mRNADOCA treatmentBlood pressureDOCA administrationExchanger isoform 1Rat aortaDOCA groupSpironolactoneAorta
2013
Role of Gap Junctions and Hemichannels in Parasitic Infections
Vega JL, Subiabre M, Figueroa F, Schalper KA, Osorio L, González J, Sáez JC. Role of Gap Junctions and Hemichannels in Parasitic Infections. BioMed Research International 2013, 2013: 589130. PMID: 24236292, PMCID: PMC3819887, DOI: 10.1155/2013/589130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial InfectionsConnexinsGap JunctionsHumansParasitic DiseasesVirus DiseasesConceptsForm gap junction channelsCell-cell interfaceDiverse physiologic processesGap junction channelsInvertebrate cellsVertebratesJunction channelsRole of CxsCell surfaceNew therapeutic designsPanx channelsHemichannelsGap junctionsTherapeutic designCellular communicationRecent findingsParasitic infectionsPhysiologic processesPathological statesPossible roleCxRecent evidenceInnexinsChannel typesPannexins
2012
Regulation of Intercellular Calcium Signaling Through Calcium Interactions with Connexin-Based Channels
Orellana J, Sánchez H, Schalper K, Figueroa V, Sáez J. Regulation of Intercellular Calcium Signaling Through Calcium Interactions with Connexin-Based Channels. Advances In Experimental Medicine And Biology 2012, 740: 777-794. PMID: 22453969, DOI: 10.1007/978-94-007-2888-2_34.Peer-Reviewed Original ResearchConceptsGap junction channelsConnexin-based channelsExtra-cellular milieuNumerous cellular eventsCell-cell interactionsMembrane proteinsMolecular basisCellular eventsIntercellular communicationJunction channelsRole of Ca2ConnexinsIntercellular calciumHemichannelsIntercellular propagationIntercellular Ca2RegulationCalcium wavesCalcium interactionCa2ProteinPathwayInteractionFamilyModulation of gap junction channels and hemichannels by growth factors
Schalper K, Riquelme M, Brañes M, Martínez A, Vega J, Berthoud V, Bennett M, Sáez J. Modulation of gap junction channels and hemichannels by growth factors. Molecular Omics 2012, 8: 685-698. PMID: 22218428, DOI: 10.1039/c1mb05294b.Peer-Reviewed Original ResearchConceptsGap junction channelsTransduction pathwaysGrowth factor signal transduction pathwaysJunction channelsNumerous cellular processesCell-cell communicationCell-cell channelsGrowth factorSignal transduction pathwaysProtein kinase-dependent mechanismNormal cellular responseCellular transduction pathwaysKinase-dependent mechanismCell membrane receptorsGap junction hemichannelsCellular coordinationCellular processesProtein kinaseCellular responsesCell stageMembrane receptorsMembrane channelsCell typesFunctional consequencesChannel insertion
2011
Cation permeation through connexin 43 hemichannels is cooperative, competitive and saturable with parameters depending on the permeant species
Orellana J, Díaz E, Schalper K, Vargas A, Bennett M, Sáez J. Cation permeation through connexin 43 hemichannels is cooperative, competitive and saturable with parameters depending on the permeant species. Biochemical And Biophysical Research Communications 2011, 409: 603-609. PMID: 21600880, PMCID: PMC3118918, DOI: 10.1016/j.bbrc.2011.05.031.Peer-Reviewed Original Research
2010
Cell membrane permeabilization via connexin hemichannels in living and dying cells
Sáez J, Schalper K, Retamal M, Orellana J, Shoji K, Bennett M. Cell membrane permeabilization via connexin hemichannels in living and dying cells. Experimental Cell Research 2010, 316: 2377-2389. PMID: 20595004, DOI: 10.1016/j.yexcr.2010.05.026.Peer-Reviewed Original ResearchConceptsCell membrane permeabilityMembrane permeabilityComplex signaling cascadesConnexin hemichannelsDiverse cell typesCx HCsGap junction channelsVertebrate cellsCell membrane permeabilizationForm hemichannelsMembrane permeabilizationSignaling cascadesOpen probabilityJunction channelsCell typesCultured cellsExtracellular microenvironmentCell membraneHemichannelsMost cellsLow open probabilityStage dependencyUnitary conductanceSmall moleculesConnexins
2009
Dysfunctions of the diffusional membrane pathways mediated by hemichannels in inherited and acquired human diseases.
Schalper K, Orellana J, Berthoud V, Sáez J. Dysfunctions of the diffusional membrane pathways mediated by hemichannels in inherited and acquired human diseases. Current Vascular Pharmacology 2009, 7: 486-505. PMID: 19485891, DOI: 10.2174/157016109789043937.Peer-Reviewed Original ResearchConceptsHuman genetic diseasesNormal cell functioningHemichannel activityMost cell typesConnexin mutantsForm homoTransmembrane proteinMembrane permeabilizationPlasma membraneLethal stimuliMembrane pathwaysCell functioningHuman diseasesCell deathCell typesGenetic diseasesMost cellsHemichannelsPannexinsSmall moleculesConnexinsTransportersPathological conditionsPathwayVertebratesModulation of Brain Hemichannels and Gap Junction Channels by Pro-Inflammatory Agents and Their Possible Role in Neurodegeneration
Orellana JA, Sáez PJ, Shoji KF, Schalper KA, Palacios–Prado N, Velarde V, Giaume C, Bennett MV, Sáez JC. Modulation of Brain Hemichannels and Gap Junction Channels by Pro-Inflammatory Agents and Their Possible Role in Neurodegeneration. Antioxidants & Redox Signaling 2009, 11: 369-399. PMID: 18816186, PMCID: PMC2713807, DOI: 10.1089/ars.2008.2130.Peer-Reviewed Original ResearchConceptsGap junction channelsJunction channelsDiverse cell typesPro-inflammatory agentsAcute inflammatory responseActivity of hemichannelsGap junctional communicationGlial hemichannelsProtein subunitsCx43 hemichannel activityGlial activationAnomalous proteinInflammatory processMembrane channelsCell typesNeuronal viabilityInflammatory responseNeuronal Cx36Astroglial networksNormal brainHemichannel activityChannel disordersHemichannelsSubthreshold stimulationATP release
2008
Currently Used Methods for Identification and Characterization of Hemichannels
Schalper K, Palacios-Prado N, Orellana J, Sáez J. Currently Used Methods for Identification and Characterization of Hemichannels. Cell Communication & Adhesion 2008, 15: 207-218. PMID: 18649191, DOI: 10.1080/15419060802014198.Peer-Reviewed Original ResearchConceptsVertebrate cellsMammalian cellsTransmembrane proteinPlasma membraneFunctional hemichannelsMolecular identityPannexin hemichannelsConnexin hemichannelsHemichannelsCommunication pathwaysSmall moleculesConnexinsNew experimental approachExperimental approachCellsPannexinsBulk of informationProteinIdentificationPathwayParacrineMembraneVivoResponseFurther studies
2007
Possible Involvement of Different Connexin43 Domains in Plasma Membrane Permeabilization Induced by Ischemia-Reperfusion
Retamal MA, Schalper KA, Shoji KF, Orellana JA, Bennett MV, Sáez JC. Possible Involvement of Different Connexin43 Domains in Plasma Membrane Permeabilization Induced by Ischemia-Reperfusion. The Journal Of Membrane Biology 2007, 218: 49-63. PMID: 17705051, DOI: 10.1007/s00232-007-9043-y.Peer-Reviewed Original ResearchOpening of connexin 43 hemichannels is increased by lowering intracellular redox potential
Retamal MA, Schalper KA, Shoji KF, Bennett MV, Sáez JC. Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 8322-8327. PMID: 17494739, PMCID: PMC1895948, DOI: 10.1073/pnas.0702456104.Peer-Reviewed Original Research