2025
Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody–Drug Conjugate TAK-500
Appleman V, Matsuda A, Ganno M, Zhang D, Rosentrater E, Lopez A, Porciuncula A, Hatten T, Christensen C, Merrigan S, Lee H, Lee M, Wang C, Dong L, Huang J, Iartchouk N, Wang J, Xu H, Yoneyama T, Piatkov K, Haridas S, Harbison C, Gregory R, Parent A, Lineberry N, Arendt C, Schalper K, Abu-Yousif A. Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody–Drug Conjugate TAK-500. Cancer Immunology Research 2025, 13: 661-679. PMID: 39918395, PMCID: PMC12046323, DOI: 10.1158/2326-6066.cir-24-0103.Peer-Reviewed Original ResearchIntratumoral myeloid cellsMyeloid cellsTumor microenvironmentImmune responseCCR2+ cellsI interferonImmunosuppressive myeloid populationsImmune activation in vitroImmune cell markersLocal immune activationMurine tumor modelsAdaptive immune responsesAntibody drug conjugatesType I interferonAntitumor immunityInnate immune responseMyeloid populationsSTING agonistsSolid tumorsCCR2 proteinImmune activationTumor modelCell markersHuman tumorsAdaptive immunity
2022
Digital spatial profiling to uncover biomarkers of immunotherapy outcomes in head and neck squamous cell carcinoma.
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Psyrri A, Rimm D. Digital spatial profiling to uncover biomarkers of immunotherapy outcomes in head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2022, 40: 6050-6050. DOI: 10.1200/jco.2022.40.16_suppl.6050.Peer-Reviewed Original ResearchNeck squamous cell carcinomaM HNSCC patientsSquamous cell carcinomaB2M expressionOverall survivalHNSCC patientsValidation cohortCell carcinomaB2MPre-treatment biopsy samplesUnivariate Cox regression modelM expressionFunctional antigen presentationHigh beta2-microglobulinTreatment of recurrentImmune checkpoint expressionCox regression modelImmune cell markersStandard of careIndependent validation cohortSpatial profiling technologyDigital spatial profilingDigital spatial profiling (DSP) technologyImmune stromaM HNSCCIntramuscular (IM) INO-5401 + INO-9012 with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma.
Reardon D, Brem S, Desai A, Bagley S, Kurz S, De La Fuente M, Nagpal S, Welch M, Hormigo A, Forsyth P, Mandel J, Khagi S, Aiken R, Walbert T, Lieberman F, Portnow J, Battiste J, Gillespie E, Lowy I, Skolnik J. Intramuscular (IM) INO-5401 + INO-9012 with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma. Journal Of Clinical Oncology 2022, 40: 2004-2004. DOI: 10.1200/jco.2022.40.16_suppl.2004.Peer-Reviewed Original ResearchPre-treatment tissueCohort AT cellsLytic potentialAntigen-specific T cellsImmune responsePost-treatment tumor tissuesFlow cytometryMedian OS durationMGMT-unmethylated patientsPD-1 inhibitorsDiagnosed GBM patientsT cell infiltrationAdverse event profileImmune-related markersImmune cell markersRobust immune responseCellular immune responsesWilcoxon rank sum testImmune response suppressionGene expressionPresence of perforinGene expression signaturesRank sum testMedian OS
2021
Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
Backman M, La Fleur L, Kurppa P, Djureinovic D, Elfving H, Brunnström H, Mattsson J, Lindberg A, Pontén V, Eltahir M, Mangsbo S, Gulyas M, Isaksson J, Jirström K, Kärre K, Leandersson K, Mezheyeuski A, Pontén F, Strell C, Lindskog C, Botling J, Micke P. Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer. The Journal Of Pathology 2021, 255: 243-256. PMID: 34339045, DOI: 10.1002/path.5772.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune cell infiltrationHigh immune cell infiltrationCell infiltrationNK cellsImmune classPlasma cellsLow immune cell infiltrationEra of immunotherapyCell lung cancerImmune cell markersTumor mutational loadImmune response-related genesInnate immune responseImmune cell analysisClinicopathologic characteristicsPD-L1Immune activationImmune classificationNSCLC casesImmune patternsLung cancerImmune cellsClinical backgroundImmune response
2020
Immunological Differences Between Immune-Rich Estrogen Receptor–Positive and Immune-Rich Triple-Negative Breast Cancers
O’Meara T, Marczyk M, Qing T, Yaghoobi V, Blenman K, Cole K, Pelekanou V, Rimm DL, Pusztai L. Immunological Differences Between Immune-Rich Estrogen Receptor–Positive and Immune-Rich Triple-Negative Breast Cancers. JCO Precision Oncology 2020, 4: po.19.00350. PMID: 32923897, PMCID: PMC7446500, DOI: 10.1200/po.19.00350.Peer-Reviewed Original ResearchER-positive breast cancerTriple-negative BCM2-like macrophagesTumor-infiltrating lymphocytesBreast cancerImmune-related genesEstrogen receptor-positive breast cancerImmuno-oncology therapeutic targetsRegulatory T cell markersReceptor-positive breast cancerTriple-negative breast cancerImmune activation markersT-cell markersImmune cell markersM1-like macrophagesDifferent immunotherapy strategiesBreast Cancer International ConsortiumNegative breast cancerImmuno-oncology trialsTGF-β pathwayAntitumor immunityCancer Genome AtlasImmunotherapy strategiesActivation markersImmune microenvironment
2019
Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile
Skaug B, Khanna D, Swindell WR, Hinchcliff ME, Frech TM, Steen VD, Hant FN, Gordon JK, Shah AA, Zhu L, Zheng WJ, Browning JL, Barron AMS, Wu M, Visvanathan S, Baum P, Franks JM, Whitfield ML, Shanmugam VK, Domsic RT, Castelino FV, Bernstein EJ, Wareing N, Lyons MA, Ying J, Charles J, Mayes MD, Assassi S. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Annals Of The Rheumatic Diseases 2019, 79: 379-386. PMID: 31767698, PMCID: PMC7386329, DOI: 10.1136/annrheumdis-2019-215894.Peer-Reviewed Original ResearchConceptsImmune cell signaturesEarly diffuse systemic sclerosisDiffuse systemic sclerosisLonger disease durationSystemic sclerosisDisease durationCell signatureSSc patientsT cellsEarly diffuse cutaneous systemic sclerosisScleroderma Outcome Study cohortDiffuse cutaneous systemic sclerosisShorter disease durationCutaneous systemic sclerosisRodnan skin scoreCD8 T cellsB cell signaturesCD4 T cellsSystemic sclerosis cohortImmune cell markersClinical trial designDiffuse SSc patientsBiopsy RNAProspective registryClinical courseSevere Leptospirosis Features in the Spleen Indicate Cellular Immunosuppression Similar to That Found in Septic Shock
Duarte-Neto A, Croda J, Pagliari C, Soriano F, Nicodemo A, Duarte M. Severe Leptospirosis Features in the Spleen Indicate Cellular Immunosuppression Similar to That Found in Septic Shock. Frontiers In Immunology 2019, 10: 920. PMID: 31114579, PMCID: PMC6503108, DOI: 10.3389/fimmu.2019.00920.Peer-Reviewed Original ResearchConceptsSeptic shockLeptospirosis patientsSevere leptospirosisPulmonary hemorrhagePositive cellsRed pulpBacterial septic shockSeptic shock patientsCaspase-3-positive cellsImmune cell markersSpleen of patientsActive caspase-3 positive cellsSemi-quantitative scoreImmunomodulatory treatmentShock patientsCellular immunosuppressionIL-10Immunologic featuresImmunosuppressive stateMarked atrophyEndothelial activationControl spleensHistological featuresIntense infiltrationPlasma cells
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