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
2021
Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity
Anfray C, Mainini F, Digifico E, Maeda A, Sironi M, Erreni M, Anselmo A, Ummarino A, Gandoy S, Expósito F, Redrado M, Serrano D, Calvo A, Martens M, Bravo S, Mantovani A, Allavena P, Andón FT. Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity. Journal For ImmunoTherapy Of Cancer 2021, 9: e002408. PMID: 34531246, PMCID: PMC8449972, DOI: 10.1136/jitc-2021-002408.Peer-Reviewed Original ResearchConceptsT cellsSingle treatmentAntitumoral efficacyImmune responseProteomics experimentsProtein-protein interaction analysisFlow cytometryM-CSF-differentiated macrophagesInteraction network analysisAntitumor immune responseRecruitment of CD4Tumor-infiltrating leukocytesAntitumoral immune responseImmunocompetent murine modelInfiltration of macrophagesQuantitative proteomics experimentsLung cancer modelMacrophage cytotoxic activityT cell proliferationTumor-associated macrophagesTLR agonist treatmentCytotoxic activityAntitumor effectorsAntitumoral immunityTumor rechallenge