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
2022
Two alternative cell line models for the study of multiorganic metastasis and immunotherapy in Lung Squamous Cell Carcinoma
Valencia K, Sainz C, Bértolo C, de Biurrun G, Agorreta J, Azpilikueta A, Larrayoz MJ, Bosco G, Zandueta C, Redrado M, Redín E, Exposito F, Serrano D, Echepare M, Ajona D, Melero I, Pio R, Thomas R, Calvo A, Montuenga LM. Two alternative cell line models for the study of multiorganic metastasis and immunotherapy in Lung Squamous Cell Carcinoma. Disease Models & Mechanisms 2022, 15: dmm049137. PMID: 34870316, PMCID: PMC8822220, DOI: 10.1242/dmm.049137.Peer-Reviewed Original ResearchConceptsLung squamous cell carcinomaSquamous cell carcinomaLUSC cell linesCell carcinomaCell linesHuman squamous cell carcinomaImmune checkpoint inhibitionAdequate mouse modelsCell line modelsCheckpoint inhibitionImmune landscapeAdrenal glandJ miceMouse modelHuman subtypesMetastatic potentialTumor cell linesCarcinomaRNA sequencingRemarkable heterogeneityHuman diseasesTranscriptomic patternsImmunotherapyMetastasisChloroethylurea
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