2024
Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy in pancreatic ductal adenocarcinoma
Kim I, Diamond M, Yuan S, Kemp S, Kahn B, Li Q, Lin J, Li J, Norgard R, Thomas S, Merolle M, Katsuda T, Tobias J, Baslan T, Politi K, Vonderheide R, Stanger B. Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy in pancreatic ductal adenocarcinoma. Nature Communications 2024, 15: 1532. PMID: 38378697, PMCID: PMC10879147, DOI: 10.1038/s41467-024-46048-7.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaEpithelial-to-mesenchymal transitionResistance to immunotherapyT cell killingDuctal adenocarcinomaAcquired resistance to immunotherapyResistance to cancer immunotherapyMouse model of pancreatic ductal adenocarcinomaModel of pancreatic ductal adenocarcinomaExpression of immune checkpointsInterferon regulatory factor 6Effect of TNF-aEMT transcription factor ZEB1Antigen presentation machineryTumor immune microenvironmentCell-intrinsic defectsPro-apoptotic effectsPresentation machineryCancer immunotherapyImmune checkpointsTumor relapseImmune microenvironmentPrimary resistanceT cellsAcquired resistance
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
2019
Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu Z, Patel K, Arnal‐Estape A, Melnick M, Politi K, Monteiro C, Zhu L, Valiente M, Kluger H, Chiang V, Nguyen D. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. The FASEB Journal 2019, 33: 368.8-368.8. DOI: 10.1096/fasebj.2019.33.1_supplement.368.8.Peer-Reviewed Original ResearchBrain tumor microenvironmentBrain metastasesTumor microenvironmentTumor cellsLung adenocarcinomaTumor lesionsBrain metastatic tumor cellsBreast cancer brain metastasesHuman tumorsExpression of TIM3Cancer brain metastasesMetastatic brain tumorsExpression of astrocytesIntra-arterial injectionTumor-associated macrophagesSyngeneic model systemModels of melanomaFull-text articlesMetastatic tumor cellsCNS metastasesNeuroinflammatory responseBrain lesionsLung tumorsT cellsAthymic mice
2017
Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers.
Datar I, Mani N, Henick B, Wurtz A, Kaftan E, Herbst R, Rimm D, Gettinger S, Politi K, Schalper K. Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers. Journal Of Clinical Oncology 2017, 35: e14611-e14611. DOI: 10.1200/jco.2017.35.15_suppl.e14611.Peer-Reviewed Original ResearchNon-small cell lung carcinomaTim-3PD-1LAG-3T cellsInhibitory receptorsAdvanced non-small cell lung carcinomaPD-1 axis blockadeHigh TIM-3Immune suppressive pathwaysImmune inhibitory receptorsCell lung carcinomaMembranous staining patternPre-treatment samplesWhole tissue sectionsWhole tumor areaClinical responseMost patientsAxis blockadeLow levelsLung carcinomaT lymphocytesMultiplex immunofluorescenceHigh levelsSuppressive pathways