2022
CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression
Zhang M, Liu ZZ, Aoshima K, Cai WL, Sun H, Xu T, Zhang Y, An Y, Chen JF, Chan LH, Aoshima A, Lang SM, Tang Z, Che X, Li Y, Rutter SJ, Bossuyt V, Chen X, Morrow JS, Pusztai L, Rimm DL, Yin M, Yan Q. CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Science Translational Medicine 2022, 14: eabf5473. PMID: 35108062, PMCID: PMC9003667, DOI: 10.1126/scitranslmed.abf5473.Peer-Reviewed Original ResearchConceptsBreast cancer metastasisReticuloendotheliosis viral oncogene homolog ACancer metastasisImmune suppressionM2 macrophagesWorse metastasis-free survivalMetastatic breast cancerMetastasis-free survivalV-rel avian reticuloendotheliosis viral oncogene homolog ACancer-related deathPrimary breast tumorsMultiple mouse modelsNF-κB signalingImmunocompetent settingNuclear factor-κB family membersMetastasis-promoting genesDistant metastasisMetastatic sitesPrimary tumorEffective therapyBreast cancerMetastasis treatmentMouse modelBreast tumorsMetastasis
2019
Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X, Han X, Archer KA, O’Neill T, Herbst RS, Boto AN, Sanmamed MF, Langermann S, Rimm DL, Chen L. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nature Medicine 2019, 25: 656-666. PMID: 30833750, PMCID: PMC7175920, DOI: 10.1038/s41591-019-0374-x.Peer-Reviewed Original ResearchConceptsNormalization cancer immunotherapyTumor microenvironmentSiglec-15Antibody blockadeCancer immunotherapyImmune suppressorMyeloid cellsAntigen-specific T cell responsesB7-H1/PDTumor-infiltrating myeloid cellsB7-H1 moleculesAnti-tumor immunityT cell responsesPotential targetImmune evasion mechanismsInhibits tumor growthMacrophage colony-stimulating factorColony-stimulating factorB7-H1Evasion mechanismsMouse modelHuman cancer cellsTumor growthCell responsesGenetic ablation
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutations
2016
RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsRas ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune response
2011
β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas
Damsky WE, Curley DP, Santhanakrishnan M, Rosenbaum LE, Platt JT, Rothberg BE, Taketo MM, Dankort D, Rimm DL, McMahon M, Bosenberg M. β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas. Cancer Cell 2011, 20: 741-754. PMID: 22172720, PMCID: PMC3241928, DOI: 10.1016/j.ccr.2011.10.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DifferentiationBenzamidesBeta CateninCell Transformation, NeoplasticColorectal NeoplasmsEnzyme ActivationGene Knockdown TechniquesHumansImatinib MesylateKaplan-Meier EstimateLung NeoplasmsLymphatic MetastasisMelanocytesMelanoma, ExperimentalMiceMice, 129 StrainMice, Inbred C57BLMice, TransgenicPhosphorylationPiperazinesProtein StabilityProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePyrimidinesSignal TransductionSkin NeoplasmsSplenic NeoplasmsTranscription, GeneticTumor Cells, CulturedConceptsΒ-catenin levelsPI3K/AktLymph nodesMetastatic tumorsFrequent metastasisTumor differentiationMalignant melanomaMAPK/ERKMelanoma metastasesMouse modelControl metastasisHuman melanomaMelanomaMetastasisΒ-catenin stabilizationPTEN lossCentral mediatorMetastasis regulatorsΒ-cateninSpecific changesFunctional implicationsWntLungProinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes
Scott KL, Nogueira C, Heffernan TP, van Doorn R, Dhakal S, Hanna JA, Min C, Jaskelioff M, Xiao Y, Wu CJ, Cameron LA, Perry SR, Zeid R, Feinberg T, Kim M, Woude G, Granter SR, Bosenberg M, Chu GC, DePinho RA, Rimm DL, Chin L. Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes. Cancer Cell 2011, 20: 92-103. PMID: 21741599, PMCID: PMC3176328, DOI: 10.1016/j.ccr.2011.05.025.Peer-Reviewed Original ResearchMeSH KeywordsAcid PhosphataseAnimalsCell LineageConserved SequenceEvolution, MolecularGene Expression ProfilingGene Expression Regulation, NeoplasticGenomeHumansIsoenzymesKaplan-Meier EstimateMelanomaMiceNeoplasm InvasivenessNeoplasm MetastasisNeoplasm StagingOncogenesPhosphorylationReproducibility of ResultsSkin NeoplasmsTartrate-Resistant Acid PhosphataseTissue Array AnalysisConceptsFunctional genetic screensGenetic screenGlobal transcriptomeMetastatic potentialSuch genesGenomic evidenceExpression selectionTranscriptomic profilesHuman melanoma tissuesMetastasis driverCell invasionKey pathwaysOncogenic capabilitiesMelanoma tissuesGenesHuman melanomaHuman primary melanomasTranscriptomeMouse modelSpontaneous metastasisOncogeneEnhancerACP5PathwayInvasion