2025
Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses
Lakshmipathi J, Santha S, Li M, Qian Y, Roy S, Luheshi N, Politi K, Bosenberg M, Eyles J, Muthusamy V. Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses. Cancer Immunology, Immunotherapy 2025, 74: 250. PMID: 40560386, PMCID: PMC12198101, DOI: 10.1007/s00262-025-04105-0.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseTumor-associated macrophagesCytotoxic T cellsImmune responseActivity of checkpoint inhibitorsAnti-PD-L1 antibodyPhagocytosis of tumor cellsAnti-PD-L1Enhanced anti-tumorAntigen presentation machineryCell-based immune responsesMurine tumor modelsTh1-type cytokinesColorectal carcinoma tumorsICI resistanceMurine IL12Checkpoint inhibitorsPresentation machineryIntratumoral deliveryResistant tumorsAdvanced diseaseCarcinoma tumorsTumor microenvironmentMurine tumorsT cellsEvaluating the immunogenicity of a mouse partial hindlimb for composite allotransplantation
Sun J, Ligi S, Biniazan F, Haykal S. Evaluating the immunogenicity of a mouse partial hindlimb for composite allotransplantation. Frontiers In Immunology 2025, 16: 1595319. DOI: 10.3389/fimmu.2025.1595319.Peer-Reviewed Original ResearchPost-operative day 7CD8+ T cellsTr1 cellsVascularized composite allotransplantationAcute rejectionT cellsAllogeneic skinImmune responseTransplantation modelIncreased CD8+ T cellsImproving long-term graft survivalRecipient-derived T cellsFlow cytometryLong-term graft survivalPhenotype of infiltrating cellsImmune response complexityTolerance induction strategiesIncreased risk of infectionImmune cell populationsT cell presenceTUNEL-positive cellsInvestigate immune responsesSevere tissue traumaImmunosuppressive approachesSubclinical rejectionToll-like receptors in B cells and obesity
Wang P, Hou C, Wong F, Wen L. Toll-like receptors in B cells and obesity. Trends In Molecular Medicine 2025 PMID: 40527636, DOI: 10.1016/j.molmed.2025.05.005.Peer-Reviewed Original ResearchToll-like receptorsPathogen-associated molecular patternsB cellsDendritic cellsFunction of Toll-like receptorsActivation of dendritic cellsActivation of TLR signalingExcessive adipose tissue accumulationSignaling mechanisms of Toll-like receptorsT cell differentiationAdipose tissue accumulationContext of obesityMechanisms of Toll-like receptorsChronic inflammationInflammatory activityAdaptive immunityImmune responseMetabolic dysregulationTLR signalingImmune functionObesityTissue accumulationMetabolic diseasesMolecular patternsSignaling mechanismsCYPD limits HR+ mammary carcinogenesis in mice
Buqué A, Beltrán-Visiedo M, Sato A, Galassi C, Petroni G, Galluzzi L. CYPD limits HR+ mammary carcinogenesis in mice. Cell Death Discovery 2025, 11: 273. PMID: 40494873, PMCID: PMC12152121, DOI: 10.1038/s41420-025-02555-0.Peer-Reviewed Original ResearchMammary carcinogenesisFemale miceImmune responseAssociated with accelerated disease progressionHormone receptorsAntigen-specific immune responsesInfluence mammary carcinogenesisTumor-associated antigensAdaptive immune responsesResistant to treatmentIn vivo modelsWild-type counterpartsReceptor-interacting serine-threonine kinase 3Medroxyprogesterone acetateVariant of cell deathLineage kinase domainHomozygous deletionBreast cancerTumor developmentDisease progressionTreatment sensitivityInflammatory reactionMicePeptidylprolyl isomerase FHuman hormone receptorsAutonomic modulation of the immune response and implications for CNS malignancies
Wachsmuth L, Srinivasan E, Puviindran B, Haskell-Mendoza A, DeSpenza T, Fecci P. Autonomic modulation of the immune response and implications for CNS malignancies. Npj Precision Oncology 2025, 9: 168. PMID: 40483275, PMCID: PMC12145445, DOI: 10.1038/s41698-025-00957-y.Peer-Reviewed Original ResearchCentral nervous systemAntitumor immune responseImmune responseAutonomic nervous systemNervous systemCentral nervous system malignanciesCentral nervous system inflammationModulation of immune responsesCentral nervous system inputImmune cell functionRegulate immune responsesIntracranial malignanciesImmune cellsMalignancyAutonomic modulationNeuro-immunologyCell functionImmune organsSignaling pathwayGlobal physiological processesTripartite interactionResponseInflammationCancerPhysiological processesRole of Chimeric Antigen Receptor–Expressing Cell Therapy in Immune-Mediated Kidney Diseases: A Review
Peng J, Zhang Y, Wang J, Zhang H, Schett G. Role of Chimeric Antigen Receptor–Expressing Cell Therapy in Immune-Mediated Kidney Diseases: A Review. American Journal Of Kidney Diseases 2025 PMID: 40484342, DOI: 10.1053/j.ajkd.2025.04.012.Peer-Reviewed Original ResearchImmune-mediated kidney diseasesB-cell depletionB cellsKidney diseaseCell therapyPlasma cellsTreatment of immune-mediated kidney diseasesB-cell-depleting monoclonal antibodyB-cell targeted therapiesComplete B-cell depletionAutoantibody-producing plasma cellsDeplete plasma cellsMonoclonal antibodiesAntigen-presenting cellsAdaptive immune responsesImmune-mediatedSelf-antigensT cellsImmune cellsImmune responseTherapyInfiltrated tissuesDiseaseAntibodiesCellsMedications for opioid use disorder shape immune responses during chronic HIV infection
Collora J, Steinhauser S, Davenport T, Lin D, Eshetu A, Zeidi S, Kim R, Frank C, Kluger Y, Springer S, Ho Y. Medications for opioid use disorder shape immune responses during chronic HIV infection. Cell Reports Medicine 2025, 6: 102159. PMID: 40460829, PMCID: PMC12208330, DOI: 10.1016/j.xcrm.2025.102159.Peer-Reviewed Original ResearchConceptsOpioid use disorderTumor necrosis factorImmune responseHIV infectionAssociated with HIV replicationCytotoxic T cell populationsRisk of opioid use disorderUse disorderPeripheral blood immune cellsI interferonChronic HIV infectionRNA expressionPartial agonist buprenorphineT cell populationsShape immune responsesBlood immune cellsType I interferonImprove immune responsesAgonist buprenorphineAgonist methadoneHIV expressionAntagonist naltrexoneHIV replicationImmune profileImmune cellsInvestigating the determinants of immunotherapy response in the primary tumor of clear cell renal cell carcinoma (RCC).
Tang C, Poduval D, Lee S, Panian J, Pandya C, Saidian A, McKay R, Braun D. Investigating the determinants of immunotherapy response in the primary tumor of clear cell renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.e16507.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaICI responseLoss of heterozygosityPrimary RCC tumorsPrimary tumorHLA evolutionary divergenceGene set enrichment analysisPost-treatment samplesRCC tumorsTumors resistant to immune checkpoint inhibitorsResistance to immune checkpoint inhibitorsTreated with immune checkpoint inhibitorsResponse to immune checkpoint inhibitorsResponse to ICI therapyAdvanced renal cell carcinomaImmune responseClear cell renal cell carcinomaSignatures of immune responsesCaris Life SciencesCell renal cell carcinomaPre-treatment tumorsSingle-sample gene set enrichment analysisDriver gene mutationsFisher's exact testThe efficacy of METTL3 inhibition in pre-clinical models of MDS and AML.
Kenworthy C, Wei M, VanOudenhove J, Busarello E, Ramirez Amarilla C, Paul S, Cruz J, Baassiri A, Maul-Newby H, Biancon G, Tebaldi T, Halene S. The efficacy of METTL3 inhibition in pre-clinical models of MDS and AML. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.e18584.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyelodysplastic syndromeInnate immune responseImmune signaturesTransplantation modelModel of myelodysplastic syndromeMurine models of leukemiaPreclinical anti-tumour efficacyImmune responseInnate immune cell subsetsSolid tumor clinical trialsSplicing factorsCompetitive transplant modelImmune checkpoint inhibitionMouse solid tumor modelsDouble-stranded RNAMyelodysplastic syndrome patientsInnate immune signaturesAnti-tumor efficacyImmune cell subsetsMyelodysplastic syndromes pathogenesisDriver genesSolid tumor modelsPre-clinical modelsModels of leukemiaA phase 1b study of combined treatment with dupilumab (anti-IL-4Ra) and cemiplimab (anti-PD-1) in patients with early-stage, resectable NSCLC.
Crowley F, Lucas N, Wu K, Wilk J, Hapanowicz O, Fitzgerald L, Park M, Rohs N, Venturini N, Yankelevitz D, Chaddha U, Harkin T, Beasley M, Nicastri D, Hakami-kermani A, Housman B, Doroshow D, Kaufman A, Merad M, Marron T. A phase 1b study of combined treatment with dupilumab (anti-IL-4Ra) and cemiplimab (anti-PD-1) in patients with early-stage, resectable NSCLC. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.tps2696.Peer-Reviewed Original ResearchResected NSCLCIL-4 signalingIL-4Potential biomarkers of responsePathologic complete response rateTumor-infiltrating myeloid cellsImmune responseResponse rateAnti-PD-1Early-stagePD-1 blockadeSafety run-inComplete response ratePathological response rateStage 1 tumorsPhase 1/2 trialEffector T cellsEvent-free survivalPre-operative treatmentStage I diseaseT cell changesBiomarkers of responseDelay of surgeryStudy of combined treatmentIL-4 receptor alphaProliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons
Pagano N, Perez G, Garcia-Milian R, Manuelidis L. Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons. PLOS ONE 2025, 20: e0323825. PMID: 40434970, PMCID: PMC12118874, DOI: 10.1371/journal.pone.0323825.Peer-Reviewed Original ResearchConceptsSeptal neuronsInnate immune responseDifferential transcriptionCreutzfeldt-Jakob disease agentCJ infectionImmune responseBind misfolded proteinsInnate immune genesIntestinal myeloid cellsRat septal neuronsArrests normal cellsDisease agentsInnate immune transcriptsCreutzfeldt-JakobModel of latent infectionAnti-viral responseCDNA libraryUnique transcriptsPeripheral human bloodLate-onset diseaseUninfected neuronsUpregulated interferonImmune genesMyeloid cellsTranscriptionWeight Loss Is Protective in Preclinical Breast Cancer Models: Interactions with the Anticancer Immune Response.
Sassoon R, Perry R. Weight Loss Is Protective in Preclinical Breast Cancer Models: Interactions with the Anticancer Immune Response. Cancer Prevention Research 2025, of1-of2. PMID: 40421602, DOI: 10.1158/1940-6207.capr-25-0168.Peer-Reviewed Original ResearchICR miceIntermittent calorie restrictionE0771 breast cancer cellsPreclinical breast cancer modelsRate of tumor growthTriple-negative breast cancerAnticancer immune responseBreast cancer modelBreast cancer cellsCancer prevention researchAntitumor immunityHigh-fat dietTumor sizeImmune dysfunctionPreclinical evidenceLean controlsPoor prognosisCancer modelsBreast cancerTumor growthOld miceObesogenic dietAdvanced ageIncreased riskImmune responseTargeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors
Patel A, Tong S, Lozada K, Awasthi A, Silverman R, Totonchy J, Yang S. Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors. Pharmaceutics 2025, 17: 691. PMID: 40574005, PMCID: PMC12196278, DOI: 10.3390/pharmaceutics17060691.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsNeuronal nitric oxide synthaseNeuronal nitric oxide synthase inhibitorActivity of immune checkpoint inhibitorsT cell activationImmune checkpoint inhibitorsAnti-melanoma activityT cellsTargeting nNOSNitric oxide synthaseCheckpoint inhibitorsIFN-gCD8<sup>+</sup>PD-1<sup>+</sup> T cellsInterleukin-2PD-1<sup>+</sup> T cellsEffects of nNOS inhibitionIL-2-secreting T cellsImmune responseMouse peripheral blood mononuclear cellsOxide synthaseAnti-PD-1Immune checkpoint blockadeMelanoma immune responsePD-1 blockadePD-L1 expressionReframing the paradigm- rethinking placental and fetal immunity
Konnikova L. Reframing the paradigm- rethinking placental and fetal immunity. Placenta 2025 PMID: 40425428, DOI: 10.1016/j.placenta.2025.05.011.Peer-Reviewed Original ResearchPreterm birthMemory T cellsFetal immunityPreterm laborT cellsImmune cellsImmune developmentImmune systemNeonatal immune cellsReducing preterm laborFetal immune systemFetal immune developmentWeeks of gestationFetal immune responseMaternal tolerancePlacental immunityFetal organsCord bloodImmune environmentInfant bloodNeonatal healthImmunological issuesNeonatal protectionPrevent complicationsImmune responseTranscriptional signatures of endothelial cells shape immune responses in cardiopulmonary health and disease
Fließer E, Jandl K, Chen S, Wang M, Schupp J, Kuebler W, Baker A, Kwapiszewska G. Transcriptional signatures of endothelial cells shape immune responses in cardiopulmonary health and disease. JCI Insight 2025, 10: e191059. PMID: 40401523, PMCID: PMC12128986, DOI: 10.1172/jci.insight.191059.Peer-Reviewed Original ResearchConceptsEndothelial cellsCardiopulmonary vasculatureImmune responseImmune cell recruitmentRegulation of immune responsesFunction of endothelial cellsImmunoregulatory roleAntigen presentationCytokine secretionCell recruitmentCardiopulmonary healthDelivery of oxygenSingle-cell RNA sequencingImmunomodulatory propertiesCardiopulmonary diseaseClearance functionDisease pathogenesisTherapy targetTranscriptional signatureEC subpopulationsImmunomodulatory activityDiseaseLungVasculatureHeartExpanding the spectrum of genetic causes of DNA-specific exonucleaseTREX1 variants in thrombotic microangiopathy
Song Z, Liu Z, Li M, Li Y, Li J, Lv J, Zhang H, Zhou X. Expanding the spectrum of genetic causes of DNA-specific exonucleaseTREX1 variants in thrombotic microangiopathy. Kidney International 2025 PMID: 40383229, DOI: 10.1016/j.kint.2025.04.014.Peer-Reviewed Original ResearchANCA-associated vasculitisThrombotic microangiopathyIgA nephropathyTREX1 variantsMicroangiopathic lesionsSpectrum of genetic causesAnti-complement therapyRegulate immune responsesPlasma exchangeMicrovascular thrombiGenome integrityC3 glomerulopathyTailored therapyEndothelial damagePathogenic variantsMicrovascular diseaseImmune regulationImmune responseGenetic causeMicroangiopathyCoagulation pathwayTherapeutic avenuesNephropathyCytosolic DNAPatientsSARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults’ responses
Nehar-Belaid D, Mejías A, Xu Z, Marches R, Yerrabelli R, Chen G, Mertz S, Ye F, Sánchez P, Tsang J, Aydillo T, Miorin L, Cupic A, García-Sastre A, Ucar D, Banchereau J, Pascual V, Ramilo O. SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults’ responses. Nature Communications 2025, 16: 4562. PMID: 40379618, PMCID: PMC12084365, DOI: 10.1038/s41467-025-59411-z.Peer-Reviewed Original ResearchConceptsResponse to SARS-CoV-2Infected infantsT cellsSARS-CoV-2B cellsCytotoxic CD8+ T cellsImmune profile of childrenISG signatureNaive CD4+ T cellsCD8+ T cellsCD4+ T cellsImmune response to SARS-CoV-2Anti-IFN autoantibodiesAntibody response to SARS-CoV-2Transitional B cellsEarly life immunityCD14+ monocytesIncreased serum concentrationsInflammasome-related moleculesInterferon-stimulated genesImmune profileImmune perturbationsSerum concentrationsInflammatory cytokinesImmune responseImpact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID
Grady C, Bhattacharjee B, Silva J, Jaycox J, Lee L, Silva Monteiro V, Sawano M, Massey D, Caraballo C, Gehlhausen J, Tabachnikova A, Mao T, Lucas C, Peña-Hernandez M, Xu L, Tzeng T, Takahashi T, Herrin J, Güthe D, Akrami A, Assaf G, Davis H, Harris K, McCorkell L, Schulz W, Griffin D, Wei H, Ring A, Guan L, Dela Cruz C, Krumholz H, Iwasaki A. Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID. Communications Medicine 2025, 5: 163. PMID: 40346201, PMCID: PMC12064684, DOI: 10.1038/s43856-025-00829-3.Peer-Reviewed Original ResearchSpike protein-specific IgGProtein-specific IgGSelf-antigensImmune response to COVID-19 vaccinationCOVID-19 vaccineAntibody responseResponse to COVID-19 vaccinationT cell expansionSARS-CoV-2-specific antibody responsesAssociated with no improvementLong COVIDAssociated with symptom improvementChest painCirculating cytokinesImmune phenotypeProspective studyImmune featuresTransient improvementPrimary seriesVaccine doseHerpes virusImmune responseSymptom improvementSignificant elevationImpact of COVID-19 vaccinationA molecular systems perspective on calcium oscillations beyond ion fluxes
Xiong D, Tong C, Wu M. A molecular systems perspective on calcium oscillations beyond ion fluxes. Current Opinion In Cell Biology 2025, 94: 102523. PMID: 40311263, PMCID: PMC12113571, DOI: 10.1016/j.ceb.2025.102523.Peer-Reviewed Original ResearchDNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities
Deshmukh M, Brooks V, Roy S, Milette S, Bosenberg M, Micevic G. DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities. Clinical Epigenetics 2025, 17: 71. PMID: 40307913, PMCID: PMC12044936, DOI: 10.1186/s13148-025-01865-5.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseImmune checkpoint moleculesT-cell phenotypeDeregulated expression of oncogenesExpression of MHCDNA methylationCell-intrinsic roleSilencing tumor suppressor genesTumor suppressor geneExpression of oncogenesCheckpoint moleculesImmunological therapiesMelanoma immunotherapyCell immunogenicityAbnormal DNA methylationTumor microenvironmentImmune cellsImproved therapiesMelanomaImmune responseMethylation-based biomarkersTherapeutic opportunitiesDeregulated expressionProliferative signalsTumor migration
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