2024
Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer
Robles-Oteíza C, Hastings K, Choi J, Sirois I, Ravi A, Expósito F, de Miguel F, Knight J, López-Giráldez F, Choi H, Socci N, Merghoub T, Awad M, Getz G, Gainor J, Hellmann M, Caron É, Kaech S, Politi K. Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer. Journal Of Experimental Medicine 2024, 222: e20231106. PMID: 39585348, DOI: 10.1084/jem.20231106.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsNon-small cell lung cancerAcquired resistanceCheckpoint inhibitorsResistant tumorsPatients treated with anti-PD-1/PD-L1 therapyAnti-PD-1/PD-L1 therapyLung cancerResistance to immune checkpoint inhibitorsAssociated with decreased progression-free survivalHypoxia activated pro-drugsTargeting hypoxic tumor regionsTreat non-small cell lung cancerAnti-CTLA-4Anti-PD-1Immune checkpoint inhibitionTumor metabolic featuresProgression-free survivalCell lung cancerResistant cancer cellsHypoxic tumor regionsMHC-II levelsRegions of hypoxiaKnock-outCheckpoint inhibitionG9a/DNMT1 co-targeting inhibits non-small cell lung cancer growth and reprograms tumor cells to respond to cancer-drugs through SCARA5 and AOX1
Exposito F, Redrado M, Serrano D, Calabuig-Fariñas S, Bao-Caamano A, Gallach S, Jantus-Lewintre E, Diaz-Lagares A, Rodriguez-Casanova A, Sandoval J, San Jose-Eneriz E, Garcia J, Redin E, Senent Y, Leon S, Pio R, Lopez R, Oyarzabal J, Pineda-Lucena A, Agirre X, Montuenga L, Prosper F, Calvo A. G9a/DNMT1 co-targeting inhibits non-small cell lung cancer growth and reprograms tumor cells to respond to cancer-drugs through SCARA5 and AOX1. Cell Death & Disease 2024, 15: 787. PMID: 39488528, PMCID: PMC11531574, DOI: 10.1038/s41419-024-07156-w.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerNon-small cell lung cancer patientsCM-272Treatment of non-small cell lung cancerReprogram tumor cellsAssociated with poor prognosisResponse to chemotherapyCell lung cancerCancer drugsMonitor tumor progressionOverexpression of G9aNSCLC cell linesLung cancer growthCancer drug sensitivityNon-small cell lung cancer growthNon-invasive biomarkersTumor volumeAntitumor efficacyTargeted therapyPoor prognosisCancer modelsTumor cellsInduce cell deathTumor progressionLung cancer
2023
PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells.
Exposito F, Redrado M, Houry M, Hastings K, Molero-Abraham M, Lozano T, Solorzano J, Sanz-Ortega J, Adradas V, Amat R, Redin E, Leon S, Legarra N, Garcia J, Serrano D, Valencia K, Robles-Oteiza C, Foggetti G, Otegui N, Felip E, Lasarte J, Paz-Ares L, Zugazagoitia J, Politi K, Montuenga L, Calvo A. PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells. Cancer Research 2023, 83: 2513-2526. PMID: 37311042, DOI: 10.1158/0008-5472.can-22-3023.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerLung squamous carcinomaAnti-PD-1 therapyRegulatory T cellsCell lung cancerImmunosuppressive microenvironmentLung cancerImmunotherapy resistanceT cellsWorse progression-free survivalCell death protein 1PTEN lossAnti-TGFβ antibodyConversion of CD4PI3K/AKT/mTOR pathwayProgression-free survivalDeath protein 1Treatment of miceImmunosuppressive tumor microenvironmentPTEN/PI3K/AKT/mTOR pathwayAKT/mTOR pathwayPD-L1TLR agonistsTumor rejectionSquamous carcinomaCancer Cell-Intrinsic Alterations Associated with an Immunosuppressive Tumor Microenvironment and Resistance to Immunotherapy in Lung Cancer
Otegui N, Houry M, Arozarena I, Serrano D, Redin E, Exposito F, Leon S, Valencia K, Montuenga L, Calvo A. Cancer Cell-Intrinsic Alterations Associated with an Immunosuppressive Tumor Microenvironment and Resistance to Immunotherapy in Lung Cancer. Cancers 2023, 15: 3076. PMID: 37370686, PMCID: PMC10295869, DOI: 10.3390/cancers15123076.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsLung cancer patientsSmall cell lung cancerCancer patientsTumor microenvironmentLung cancerEffects of ICIsEfficacy of ICIsChimeric antigen receptor cellsCell lung cancer patientsCytotoxic T cellsImmunosuppressive tumor microenvironmentCell-extrinsic mechanismsCell-intrinsic alterationsGreat clinical successLack of responseCheckpoint inhibitorsICI responseTherapeutic responseT cellsDNA damage repair pathwaysClinical successImmunotherapyMetabolic alterationsTherapeutic interventions
2022
YES1 Is a Druggable Oncogenic Target in SCLC
Redin E, Garrido-Martin EM, Valencia K, Redrado M, Solorzano JL, Carias R, Echepare M, Exposito F, Serrano D, Ferrer I, Nunez-Buiza A, Garmendia I, García-Pedrero JM, Gurpide A, Paz-Ares L, Politi K, Montuenga LM, Calvo A. YES1 Is a Druggable Oncogenic Target in SCLC. Journal Of Thoracic Oncology 2022, 17: 1387-1403. PMID: 35988891, DOI: 10.1016/j.jtho.2022.08.002.Peer-Reviewed Original ResearchConceptsSubpopulation of patientsOncogenic targetsPatient-derived xenograftsMarked antitumor activityGain/amplificationPlasma-derived exosomesDistant metastasisIndependent predictorsTargetable oncogenesPoor prognosisAggressive subtypeClinical managementLung cancerPharmacologic blockadeTumor regressionMouse modelTumor growthPlasma exosomesMolecular subgroupsPharmacologic inhibitionMetastasisAntitumor activityFunctional experimentsOrganoid modelsClinical samples
2020
Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade
Ajona D, Ortiz-Espinosa S, Lozano T, Exposito F, Calvo A, Valencia K, Redrado M, Remírez A, Lecanda F, Alignani D, Lasarte J, Macaya I, Senent Y, Bértolo C, Sainz C, Gil-Bazo I, Eguren-Santamaría I, Lopez-Picazo J, Gonzalez A, Perez-Gracia J, de Andrea C, Vicent S, Sanmamed M, Montuenga L, Pio R. Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade. Nature Cancer 2020, 1: 75-85. PMID: 35121837, DOI: 10.1038/s43018-019-0007-9.Peer-Reviewed Original ResearchConceptsPD-1 blockadeCell death protein 1 (PD-1) pathwayPD-1 immune checkpoint blockadeCD8/Treg ratioHigh IGF-1R expressionInsulin-like growth factor-1Cell lung cancer treatmentIGF-1 levelsPD-1 inhibitionImmune checkpoint blockadeTumor-specific immunityCell lung cancerIGF-1R expressionHigher plasma levelsLung cancer progressionLung cancer treatmentIGF-1 receptorGrowth factor-1Protein 1 pathwayTreg ratioCD8 cellsCheckpoint blockadePD-1Syngeneic modelLung cancer
2016
Development of biological tools to assess the role of TMPRSS4 and identification of novel tumor types with high expression of this prometastatic protein.
Villalba M, Lopez L, Redrado M, Ruiz T, de Aberasturi AL, de la Roja N, Garcia D, Exposito F, de Andrea C, Alvarez-Fernandez E, Montuenga L, Rueda P, Rodriguez MJ, Calvo A. Development of biological tools to assess the role of TMPRSS4 and identification of novel tumor types with high expression of this prometastatic protein. Histology And Histopathology 2016, 32: 929-940. PMID: 27995596, DOI: 10.14670/hh-11-857.Peer-Reviewed Original ResearchConceptsTissue microarrayTMPRSS4 protein expressionProtein expressionLarge cell carcinomaNovel tumor typesCancer tissue microarraySquamous carcinomaPoor prognosisCell carcinomaAggressive tumorsCancer deathLung cancerMetastatic spreadDifferent tissue microarraysClinical valueTherapeutic targetTumor typesClinical settingRabbit polyclonal antiserumCancer typesType II serine proteaseHigh expressionTMPRSS4CarcinomaCancer