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
2018
Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement
Johnson DB, Nixon MJ, Wang Y, Wang DY, Castellanos E, Estrada MV, Ericsson-Gonzalez PI, Cote CH, Salgado R, Sanchez V, Dean PT, Opalenik SR, Schreeder DM, Rimm DL, Kim JY, Bordeaux J, Loi S, Horn L, Sanders ME, Ferrell PB, Xu Y, Sosman JA, Davis RS, Balko JM. Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement. JCI Insight 2018, 3: e120360. PMID: 30568030, PMCID: PMC6338319, DOI: 10.1172/jci.insight.120360.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, NeutralizingAntigens, CDBreast NeoplasmsCD4-Positive T-LymphocytesCell Line, TumorHistocompatibility Antigens Class IIHLA-DR AntigensHumansImmunotherapyKiller Cells, NaturalLigandsLymphocyte Activation Gene 3 ProteinMiceProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellReceptors, Cell SurfaceT-LymphocytesTumor MicroenvironmentConceptsMHC-II expressionT cellsAnti-PD-1 therapyTumor cellsPD-1 pathwayTumor-intrinsic factorsPD-1-targeted immunotherapiesMHC-II receptorsDurable responsesPD-1Immune activationImmunotherapy targetPreclinical modelsLAG-3TumorsUnique patternMHCEnhanced expressionInhibitory functionAdaptive resistanceNovel inhibitory functionImmunotherapyPatientsContext-dependent mechanismsCellsExceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic options
1996
Expression of a candidate cadherin in T lymphocytes.
Cepek KL, Rimm DL, Brenner MB. Expression of a candidate cadherin in T lymphocytes. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 6567-6571. PMID: 8692857, PMCID: PMC39065, DOI: 10.1073/pnas.93.13.6567.Peer-Reviewed Original ResearchConceptsCell adhesion eventsV8 protease digestionHuman T-cell leukemic cell lineT-cell leukemic cell lineCytoplasmic domainHomotypic adhesion moleculeCadherinLeukemic cell linesAdhesion eventsMolecular massProtease digestionHomotypic adhesionHeterotypic adhesionE-cadherinPeptide mapsSpeciesCell linesEpithelial cellsWider roleMucosal epithelial cellsAdhesion moleculesIntestinal intraepithelial T lymphocytesPan-cadherinCellsSolid tissues
1994
Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin
Cepek K, Shaw S, Parker C, Russell G, Morrow J, Rimm D, Brenner M. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. Nature 1994, 372: 190-193. PMID: 7969453, DOI: 10.1038/372190a0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCadherinsCell AdhesionCell LineHumansIntegrinsIntestinal MucosaL CellsMiceRecombinant ProteinsT-LymphocytesConceptsIntraepithelial lymphocytesAdhesion moleculesT cellsIntestinal intra-epithelial lymphocytesEpithelial cellsIntestinal intraepithelial lymphocytesIntra-epithelial lymphocytesMucosal immune systemE-cadherinTissue-specific retentionTissue-specific compartmentalizationLymphoid structuresT lymphocytesImmune systemLymphocyte homingLymphocytesΑEβ7