2023
IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling
Singh D, Carcamo S, Farias E, Hasson D, Zheng W, Sun D, Huang X, Cheung J, Nobre A, Kale N, Sosa M, Bernstein E, Aguirre-Ghiso J. 5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling. Cell Reports 2023, 42: 112560. PMID: 37267946, PMCID: PMC10592471, DOI: 10.1016/j.celrep.2023.112560.Peer-Reviewed Original ResearchConceptsDisseminated cancer cellsCancer cellsDNA methylation inhibitorNon-proliferative stateAnti-proliferative functionTranscriptional reprogrammingChromatin remodelingRetinoic acid receptorsTranscriptional programsMethylation inhibitorGrowth factor βMicroenvironmental signalsSMAD4 knockdownBreast cancer cellsDormancySuppress metastasisRARα-specific agonistLung metastasis formationNeck squamous cell carcinomaReprogrammingRetinoic acidSquamous cell carcinomaTrans retinoic acidFactor βMetastasis formation
2021
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2
Nobre A, Risson E, Singh D, Di Martino J, Cheung J, Wang J, Johnson J, Russnes H, Bravo-Cordero J, Birbrair A, Naume B, Azhar M, Frenette P, Aguirre-Ghiso J. Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2. Nature Cancer 2021, 2: 327-339. PMID: 34993493, PMCID: PMC8730384, DOI: 10.1038/s43018-021-00179-8.Peer-Reviewed Original ResearchConceptsMesenchymal stem cellsDTC dormancyHematopoietic stem cell quiescenceStem cellsStem cell quiescenceBone morphogenetic proteinTGF-β2Niche homeostasisMorphogenetic proteinsCell quiescenceBone marrow microenvironmentGenetic depletionP27 inductionDormancyConditional knockoutMarrow microenvironmentMetastatic outgrowthEstrogen receptor-positive BCExtrinsic factorsGrowth factorCellsTumor cellsBone relapseSystemic recurrenceBreast cancer
2020
Inducible de novo expression of neoantigens in tumor cells and mice
Damo M, Fitzgerald B, Lu Y, Nader M, William I, Cheung JF, Connolly KA, Foster GG, Akama-Garren E, Lee DY, Chang GP, Gocheva V, Schmidt LM, Boileve A, Wilson JH, Cui C, Monroy I, Gokare P, Cabeceiras P, Jacks T, Joshi NS. Inducible de novo expression of neoantigens in tumor cells and mice. Nature Biotechnology 2020, 39: 64-73. PMID: 32719479, PMCID: PMC7854852, DOI: 10.1038/s41587-020-0613-1.Peer-Reviewed Original ResearchConceptsT cell responsesLevel of regulationRNA splicingDNA recombinationGenetic regulationTolerance mechanismsInducible expressionNeoantigen expressionCell responsesNaïve T-cell responsesCD4 T cell responsesTumor cell linesPeripheral tolerance mechanismsT cell toleranceCentral T cell toleranceCell linesExpressionNovo expressionTight controlEndogenous CD8Antitumor immunityPeripheral toleranceAutoimmune diseasesT cellsThymus results
2017
Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments
Fluegen G, Avivar-Valderas A, Wang Y, Padgen MR, Williams JK, Nobre A, Calvo V, Cheung JF, Bravo-Cordero JJ, Entenberg D, Castracane J, Verkhusha V, Keely PJ, Condeelis J, Aguirre-Ghiso JA. Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nature Cell Biology 2017, 19: 120-132. PMID: 28114271, PMCID: PMC5342902, DOI: 10.1038/ncb3465.Peer-Reviewed Original ResearchConceptsBreast cancer cellsDormant DTCsTumor hypoxic microenvironmentTumor cellsHypoxic microenvironmentCancer cellsDisseminated tumor cellsPrimary tumor microenvironmentDisease relapsePoor prognosisTarget organsP27 inductionTransgenic miceSolid tumorsTumor microenvironmentHypoxia genesHypoxiaPhenotypic heterogeneityMicroenvironmentCellsChemotherapyRelapseHNSCCPrognosisTherapy