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 carcinoma
2021
SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation
Redin E, Garmendia I, Lozano T, Serrano D, Senent Y, Redrado M, Villalba M, De Andrea CE, Exposito F, Ajona D, Ortiz-Espinosa S, Remirez A, Bertolo C, Sainz C, Garcia-Pedrero J, Pio R, Lasarte J, Agorreta J, Montuenga LM, Calvo A. SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation. Journal For ImmunoTherapy Of Cancer 2021, 9: e001496. PMID: 33658304, PMCID: PMC7931761, DOI: 10.1136/jitc-2020-001496.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDasatinibDrug Resistance, NeoplasmFemaleHumansImmune Checkpoint InhibitorsLung NeoplasmsLymphocytes, Tumor-InfiltratingMiceMice, 129 StrainPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins c-yesSignal TransductionT-Lymphocytes, RegulatoryTumor MicroenvironmentConceptsNon-small cell lung cancerNumber of TregsMultiplex immunofluorescenceAntiprogrammed cell death 1 (PD-1) antibodySrc family kinase (SFK) inhibitor dasatinibTumor growthInhibitor dasatinibCell death 1 antibodyYES1 expressionDeath-1 antibodyImmune cytotoxic activityPD-1 treatmentPD-1/Treg cell conversionUse of dasatinibVivo depletion experimentsAntitumor activityImmune checkpoint inhibitorsOutcomes of patientsProtein expressionCohort of patientsManagement of patientsCell lung cancerRelevant mouse modelVivo drug testing