María Villalba Esparza
Associate Research Scientist in PathologyAbout
Research
Publications
2026
Safety, Feasibility, and Pharmacodynamic Activity of Intratumoral Injections of the Agonist Anti-CD137 (4-1BB) mAb Urelumab in Combination with Nivolumab.
Sanmamed M, de Andrea C, Ruiz-Guillamón D, Rodriguez-Ruiz M, Ortego I, Eguren-Santamaría I, Benito A, López-Janeiro A, Gonzalez Gomariz J, Villalba-Esparza M, Molina A, Krasko A, Ponz-Sarvise M, Lopez-Picazo J, Gomis G, Molero-Glez P, Alexandru R, Pérez-Domínguez P, Rodriguez I, Sánchez-Gregorio S, Perez-Gracia J, Melero I. Safety, Feasibility, and Pharmacodynamic Activity of Intratumoral Injections of the Agonist Anti-CD137 (4-1BB) mAb Urelumab in Combination with Nivolumab. Clinical Cancer Research 2026, 32: 1036-1045. PMID: 41543348, DOI: 10.1158/1078-0432.ccr-25-2502.Peer-Reviewed Original ResearchIntratumoral deliveryIntratumoral injectionAnti-CD137Associated with durable clinical benefitTumor-infiltrating CD8 T cellsPharmacodynamic activityPD-1/PD-L1 blockadeAgonistic anti-CD137Durable clinical benefitT lymphocyte densityDisease control rateDose-escalation cohortsT-cell-activating cytokinesCD8 T cellsFresh tumor biopsiesIntravenous nivolumabCD137 expressionTumor biopsiesSerial biopsyIntravenous dosePharmacodynamic changesPeripheral bloodClinical benefitT cellsSolid tumors
2025
Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach
Lopez de Rodas M, Villalba-Esparza M, Sanmamed M, Chen L, Rimm D, Schalper K. Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach. Nature Reviews Clinical Oncology 2025, 22: 163-181. PMID: 39820025, DOI: 10.1038/s41571-024-00984-x.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesImmune-checkpoint inhibitorsTumor-infiltrating lymphocyte subpopulationsClinical significance of tumor-infiltrating lymphocytesPredictive value of tumor-infiltrating lymphocytesSignificance of tumor-infiltrating lymphocytesStudy of tumor-infiltrating lymphocytesImmune-checkpoint inhibitor therapyImmune-mediated tumor eliminationEra of immunotherapyT cell dysfunctionBiomarkers of responseSolid tumor typesImmunotherapeutic approachesAntigen-reactiveTumor microenvironmentTumor typesClinical outcomesTumor eliminationClinical significanceSingle-cell transcriptomicsPredictive valueAnticancer mechanismClinical implicationsResistance mechanisms
2024
CD70 Deregulation in Follicular Lymphoma at Diagnosis Is Associated with Relapse and Opens New Avenues for Dual CD19-CD70 CAR-T Therapy
Araujo-Ayala F, Ros M, Bachiller M, Alexandru R, Mozas P, Colell S, Mateos-Jaimez J, López C, Villalba-Esparza M, Nadeu F, Rivero A, Dobaño-López C, Valero J, Serrat N, Gimenez-Alejandre M, Giró A, Hodson D, Lopez-Guillermo A, Campo E, Colomer D, Maiques-Diaz A, Martin-Subero J, Bea S, Magnano L, Guedan S, De Andrea C, Galan P. CD70 Deregulation in Follicular Lymphoma at Diagnosis Is Associated with Relapse and Opens New Avenues for Dual CD19-CD70 CAR-T Therapy. Blood 2024, 144: 333. DOI: 10.1182/blood-2024-199167.Peer-Reviewed Original ResearchProgression-free survivalAssociated with inferior progression-free survivalInferior progression-free survivalCAR-TFollicular lymphomaHigh-risk patientsT cellsTumor cellsFL pathogenesisCD70 expressionFL patientsCD4+Relapse groupTransformation to aggressive lymphomaCell linesIndolent B-cell lymphomaCD8+ T cellsT Follicular Helper CellsPrognosis potentialFraction of T cellsCAR-T cellsCAR-T therapyResponse to proliferative stimuliMedian Follow-UpNon-relapse group
2023
Weakly supervised deep learning to predict recurrence in low-grade endometrial cancer from multiplexed immunofluorescence images
Jiménez-Sánchez D, López-Janeiro Á, Villalba-Esparza M, Ariz M, Kadioglu E, Masetto I, Goubert V, Lozano M, Melero I, Hardisson D, Ortiz-de-Solórzano C, de Andrea C. Weakly supervised deep learning to predict recurrence in low-grade endometrial cancer from multiplexed immunofluorescence images. Npj Digital Medicine 2023, 6: 48. PMID: 36959234, PMCID: PMC10036616, DOI: 10.1038/s41746-023-00795-x.Peer-Reviewed Original ResearchEarly-stage endometrial cancerT cellsEndometrial cancerLow-grade endometrial cancerCD8+ T cellsPD-L1/PD-1Regulatory T cellsRisk of recurrenceArea under the curveTumor recurrencePrognostic factorsMolecular subtypesMultiplex immunofluorescenceTumor cellsLow-gradeRecurrenceMultiplexed immunofluorescence imagesProtein expressionTumorFoxp3Tissue areaConfidence intervalsTumor coreImmunofluorescence imagingCancerSpatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury
Cross A, de Andrea C, Villalba-Esparza M, Landecho M, Cerundolo L, Weeratunga P, Etherington R, Denney L, Ogg G, Ho L, Roberts I, Hester J, Klenerman P, Melero I, Sansom S, Issa F. Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury. JCI Insight 2023, 8: e157837. PMID: 36472908, PMCID: PMC9977306, DOI: 10.1172/jci.insight.157837.Peer-Reviewed Original ResearchConceptsAssociated with inductionCytotoxic lymphocytesLung tissueRecruitment of CXCR3Cohort of patientsCOVID-19 pneumonitisInduction of chemokinesSevere lung damageExpression of IFNGPro-inflammatory macrophagesSevere tissue damageImmune cellsInterpatient heterogeneityLung damageTherapeutic strategiesStromal cellsTissue injuryHistopathological damageTissue damageTissue pathologyGene expression dataSeveral tissuesLung samplesLymphocytesPatients
2022
Cell‐Specific Dysregulation of Iron and Oxygen Homeostasis as a Novel Pathophysiology in PSP
Lee S, Martinez‐Valbuena I, de Andrea C, Villalba‐Esparza M, Ilaalagan S, Couto B, Visanji N, Lang A, Kovacs G. Cell‐Specific Dysregulation of Iron and Oxygen Homeostasis as a Novel Pathophysiology in PSP. Annals Of Neurology 2022, 93: 431-445. PMID: 36309960, DOI: 10.1002/ana.26540.Peer-Reviewed Original ResearchConceptsAssociated with tau pathologyTau pathologyPSP pathogenesisDysregulated expressionOxygen homeostasisProgressive supranuclear palsyAbnormal iron levelsIron homeostasisMRNA transcriptsExpression of alphaIron accumulationBrain iron accumulationCell typesNeurodegenerative diseasesMolecular pathwaysDysregulation of ironBeta-hemoglobinNeurodegenerative brainHomeostasisGene expression associated with agingPSP brainsProgressive supranuclear palsy pathologyPathwayTherapy developmentSupranuclear palsyIL-6/STAT3 signaling in tumor cells restricts the expression of frameshift-derived neoantigens by SMG1 induction
Meraviglia-Crivelli D, Villanueva H, Zheleva A, Villalba-Esparza M, Moreno B, Menon A, Calvo A, Cebollero J, Barainka M, de los Mozos I, Huesa-Berral C, Pastor F. IL-6/STAT3 signaling in tumor cells restricts the expression of frameshift-derived neoantigens by SMG1 induction. Molecular Cancer 2022, 21: 211. PMID: 36443756, PMCID: PMC9703761, DOI: 10.1186/s12943-022-01679-6.Peer-Reviewed Original ResearchConceptsMalignant cellsImmune responseImmunoediting mechanismsTumor neoantigensTumor microenvironmentImmune forcesIL-6/STAT3 signalingNonsense-mediated mRNA decayImmunosuppressive tumor microenvironmentMutation-derived neoantigensTumor immune infiltrationMurine tumor modelsCancer immunotherapyTumor immunityImmune infiltrationTumor mutationsScRNAseq datasetsPancreatic cancerCytokine screenNonsense-mediated mRNA decay inhibitionTumor cellsTumor modelTumor progressionSMG1 expressionNeoantigens844 Combined immunotherapy efficacy on a multifocal hepatocellular carcinoma model based on hydrodynamic oncogene transfer
Ochoa M, Sanchez-Gregorio S, Teijeira A, Garasa S, Andrea C, Villalba M, Etxeberria I, Melero I. 844 Combined immunotherapy efficacy on a multifocal hepatocellular carcinoma model based on hydrodynamic oncogene transfer. 2022, a882-a882. DOI: 10.1136/jitc-2022-sitc2022.0844.Peer-Reviewed Original ResearchThe association between the tumor immune microenvironments and clinical outcome in low‐grade, early‐stage endometrial cancer patients
López‐Janeiro Á, Villalba‐Esparza M, Brizzi M, Jiménez‐Sánchez D, Ruz‐Caracuel I, Kadioglu E, Masetto I, Goubert V, Garcia‐Ros D, Melero I, Peláez‐García A, Hardisson D, de Andrea C. The association between the tumor immune microenvironments and clinical outcome in low‐grade, early‐stage endometrial cancer patients. The Journal Of Pathology 2022, 258: 426-436. PMID: 36169332, PMCID: PMC9828119, DOI: 10.1002/path.6012.Peer-Reviewed Original ResearchConceptsCD8+ T cellsImmune microenvironmentPD-L1T cellsLow-gradeClinical outcomesTumor cellsLack of CD8+ T cellsEarly-stage endometrial cancer patientsCD8+ T cell infiltrationFoxp3+ regulatory T cellsEarly-stage endometrial cancerExpression of PD-L1PD-L1 expression levelsFrequent expressionEarly-stage endometrial carcinomaCD8+ infiltrationMultiplexed quantitative immunofluorescencePD-L1 markersT cell infiltrationTumor immune microenvironmentRegulatory T cellsAdjuvant radiotherapy treatmentCD68+ macrophagesEndometrial cancer patientsTranslation of a tissue epigenetic signature to circulating free DNA suggests BCAT1 as a potential noninvasive diagnostic biomarker for lung cancer
Palanca-Ballester C, Hervas D, Villalba M, Valdes-Sanchez T, Garcia D, Alcoriza-Balaguer M, Benet M, Martinez-Tomas R, Briones-Gomez A, Galbis-Caravajal J, Calvo A, Juan O, Lahoz A, Cases E, Sandoval J. Translation of a tissue epigenetic signature to circulating free DNA suggests BCAT1 as a potential noninvasive diagnostic biomarker for lung cancer. Clinical Epigenetics 2022, 14: 116. PMID: 36123616, PMCID: PMC9487112, DOI: 10.1186/s13148-022-01334-3.Peer-Reviewed Original ResearchConceptsCirculating free DNALung cancer patientsDigital droplet PCRNoninvasive diagnostic biomarkersCurative treatmentDiagnostic efficacyCirculating DNALung cancerDiagnostic performanceCancer patientsPulmonary fluidDroplet PCRDNA methylation levelsMolecular biomarkersNoninvasive detectionDiagnostic biomarkersEpigenetic signaturesMethylation levelsPatientsLungFree DNABiomarkersBCAT1