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
2021
Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade
Berry S, Giraldo NA, Green BF, Cottrell TR, Stein JE, Engle EL, Xu H, Ogurtsova A, Roberts C, Wang D, Nguyen P, Zhu Q, Soto-Diaz S, Loyola J, Sander IB, Wong PF, Jessel S, Doyle J, Signer D, Wilton R, Roskes JS, Eminizer M, Park S, Sunshine JC, Jaffee EM, Baras A, De Marzo AM, Topalian SL, Kluger H, Cope L, Lipson EJ, Danilova L, Anders RA, Rimm DL, Pardoll DM, Szalay AS, Taube JM. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade. Science 2021, 372 PMID: 34112666, PMCID: PMC8709533, DOI: 10.1126/science.aba2609.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD8 AntigensFemaleFluorescent Antibody TechniqueForkhead Transcription FactorsHumansImmune Checkpoint ProteinsMacrophagesMaleMelanomaMiddle AgedPrognosisProgrammed Cell Death 1 ReceptorProgression-Free SurvivalReceptors, Cell SurfaceSingle-Cell AnalysisSOXE Transcription FactorsT-Lymphocyte SubsetsTreatment OutcomeTumor MicroenvironmentConceptsAnti-programmed cell death 1Anti-PD-1 blockadePD-1 blockadeCell death 1Tissue-based biomarkersLong-term survivalTumor tissue sectionsDeath-1PD-1PD-L1Immunoregulatory moleculesT cellsIndependent cohortMyeloid cellsMelanoma specimensMultiple cell typesTissue sectionsLow/BlockadeCell typesDistinct expression patternsExpression patternsImagingCD8Foxp3Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas
Yeung J, Yaghoobi V, Miyagishima D, Vesely MD, Zhang T, Badri T, Nassar A, Han X, Sanmamed MF, Youngblood M, Peyre M, Kalamarides M, Rimm DL, Gunel M, Chen L. Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas. Neuro-Oncology 2021, 23: 1922-1935. PMID: 33914067, PMCID: PMC8563319, DOI: 10.1093/neuonc/noab075.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1Myeloid cellsMalignant meningiomasTumor microenvironmentCSF1/CSF1RRNA-seqRNA sequencingHuman meningiomasImmune subsetsGene expressionT cellsTreatment strategiesNormalization cancer immunotherapyImportant regulatorCell typesNovel immunocompetent murine modelDeath ligand 1 (PD-L1) expressionCell death receptor-1Immunosuppressive myeloid cellsDeath receptor-1Ligand 1 expressionFactor 1Immune cell typesImmunocompetent murine modelEffective treatment strategiesSpatially Resolved and Quantitative Analysis of the Immunological Landscape in Human Meningiomas
Yeung J, Yaghoobi V, Aung TN, Vesely MD, Zhang T, Gaule P, Gunel M, Rimm DL, Chen L. Spatially Resolved and Quantitative Analysis of the Immunological Landscape in Human Meningiomas. Journal Of Neuropathology & Experimental Neurology 2021, 80: 150-159. PMID: 33393633, DOI: 10.1093/jnen/nlaa152.Peer-Reviewed Original ResearchConceptsPD-L1 expressionT cell infiltrationPD-L1PD-L2Human meningiomasTumor-infiltrating immune cell populationsHigh PD-L1 expressionT-cell activation/proliferationActivation/dysfunctionLevels of CD3Immune cell subsetsT-cell phenotypeImmune cell populationsHigh-grade tumorsActivation/proliferationHigher CD3TIL infiltrationCD8 ratioImmunotherapeutic strategiesCell subsetsImmunological statusGrade tumorsImmunological landscapeTissue microarrayMacrophage phenotype
2020
PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expressionBiomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling
Zugazagoitia J, Gupta S, Liu Y, Fuhrman K, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling. Clinical Cancer Research 2020, 26: 4360-4368. PMID: 32253229, PMCID: PMC7442721, DOI: 10.1158/1078-0432.ccr-20-0175.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-1 checkpoint blockadeCell lung cancerCheckpoint blockadeLung cancerAdvanced non-small cell lung cancerUnivariate unadjusted analysisProgression-free survivalImmune cell countsMinority of patientsRobust predictive biomarkersBiomarkers of responseLarge independent cohortsSpatial profiling technologyDigital spatial profilingDigital spatial profiling (DSP) technologyOverall survivalClinical outcomesImmune predictorsHigher CD56NSCLC casesPredictive biomarkersUnadjusted analysesImmune parametersTissue microarrayImmune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Liu Y, Zugazagoitia J, Ahmed FS, Henick BS, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy. Clinical Cancer Research 2020, 26: 970-977. PMID: 31615933, PMCID: PMC7024671, DOI: 10.1158/1078-0432.ccr-19-1040.Peer-Reviewed Original ResearchConceptsPD-L1 expressionHigh PD-L1 expressionPD-L1 levelsPD-L1Immune cellsTumor cellsT cellsHigh PD-L1 levelsPredominant immune cell typeNon-small cell lung cancer (NSCLC) casesDifferent immune cell subsetsCell lung cancer casesElevated PD-L1High PD-L1Better overall survivalDeath ligand 1Natural killer cellsImmune cell subsetsMultiple immune cellsCytotoxic T cellsLung cancer casesImmune cell typesCD68 levelsCell typesBlockade therapy
2019
Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response
Sahraei M, Chaube B, Liu Y, Sun J, Kaplan A, Price NL, Ding W, Oyaghire S, García-Milian R, Mehta S, Reshetnyak YK, Bahal R, Fiorina P, Glazer PM, Rimm DL, Fernández-Hernando C, Suárez Y. Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response. Journal Of Clinical Investigation 2019, 129: 5518-5536. PMID: 31710308, PMCID: PMC6877327, DOI: 10.1172/jci127125.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesMiR-21 expressionTumor growthMiR-21Immune responseCytotoxic T cell responsesC motif chemokine 10Antitumor immune responseT cell responsesAntitumoral immune responseTumor immune infiltratesInduction of cytokinesPotential therapeutic implicationsMiR-21 inhibitionStages of carcinogenesisAngiostatic phenotypeTumor cell deathIL-12Immune infiltratesTherapeutic implicationsSolid tumorsTumor neovascularizationTumor progressionTumor microenvironmentTumor pathogenesisSiglec-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
CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers
Pelekanou V, Villarroel-Espindola F, Schalper KA, Pusztai L, Rimm DL. CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers. Breast Cancer Research 2018, 20: 154. PMID: 30558648, PMCID: PMC6298021, DOI: 10.1186/s13058-018-1076-x.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic AgentsBiomarkers, TumorBreastBreast NeoplasmsDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMatrix Metalloproteinase 9Middle AgedPatient SelectionPrognosisReceptors, Cell SurfaceReceptors, EstrogenRetrospective StudiesSurvival AnalysisTissue Array AnalysisTumor MicroenvironmentConceptsTumor-associated macrophagesOverall survivalQuantitative immunofluorescenceMacrophage markersBreast cancerHigh expressionPan-macrophage marker CD68Triple-negative breast cancerCD163/CD68Multiplexed quantitative immunofluorescenceImproved overall survivalProtein expressionWorse overall survivalPoor overall survivalMMP-9 protein expressionSubclass of patientsMacrophage-targeted therapiesMatrix metalloproteinase-9Tissue microarray formatMMP-9 proteinBreast tumor microenvironmentModulator of responseParaffin-embedded tissuesBreast cancer biomarkersCohort B
2014
Macrophage expression of tartrate-resistant acid phosphatase as a prognostic indicator in colon cancer
How J, Brown JR, Saylor S, Rimm DL. Macrophage expression of tartrate-resistant acid phosphatase as a prognostic indicator in colon cancer. Histochemistry And Cell Biology 2014, 142: 195-204. PMID: 24429833, PMCID: PMC4101067, DOI: 10.1007/s00418-014-1181-6.Peer-Reviewed Original ResearchMeSH KeywordsAcid PhosphataseAdenocarcinomaAdultAgedAged, 80 and overAntigens, CDAntigens, Differentiation, MyelomonocyticBiomarkers, TumorColonic NeoplasmsFemaleHumansIsoenzymesMacrophagesMaleMiddle AgedReceptors, Cell SurfaceTartrate-Resistant Acid PhosphataseTissue Array AnalysisTreatment OutcomeYoung AdultConceptsColorectal cancer patientsMacrophage expressionResistant acid phosphataseColon cancerCancer patientsTRAP expressionYale-New Haven HospitalDisease-specific deathPan-macrophage markerRisk reductionPrognostic indicatorCancer survivalColorectal adenocarcinomaM2 markersImproved outcomesTissue microarrayImmunohistochemical analysisSecond cohortSurvival analysisPatientsPotential biomarkersQuantitative immunofluorescenceCancerAcid phosphataseOld cases