2024
Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer
Jeevanandam A, Yin Z, Connolly K, Joshi N. Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer. Methods In Molecular Biology 2024, 2864: 57-76. PMID: 39527217, DOI: 10.1007/978-1-0716-4184-2_4.Peer-Reviewed Original ResearchConceptsTertiary lymphoid structuresTertiary lymphoid structure formationSecondary lymphoid organsLymphoid structuresMurine modelFeatures of tertiary lymphoid structuresFunction of tertiary lymphoid structuresMouse modelPersistent inflammatory stimulationAssociated with positive clinical outcomesTissue-specific regulatory mechanismsPositive clinical outcomesPrognostic significanceClinical outcomesGut environmentNonlymphoid tissuesLymphoid aggregatesLymphoid organsMouse lungCancer patientsGenetic sequencesInflammatory stimulationRegulatory mechanismsTherapeutic modulationClinical effortsIntestinal tuft cell immune privilege enables norovirus persistence
Strine M, Fagerberg E, Darcy P, Barrón G, Filler R, Alfajaro M, D'Angelo-Gavrish N, Wang F, Graziano V, Menasché B, Damo M, Wang Y, Howitt M, Lee S, Joshi N, Mucida D, Wilen C. Intestinal tuft cell immune privilege enables norovirus persistence. Science Immunology 2024, 9: eadi7038. PMID: 38517952, PMCID: PMC11555782, DOI: 10.1126/sciimmunol.adi7038.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsIntestinal tuft cellsT cellsTufted cellsViral persistenceSite of viral persistenceChemosensory epithelial cellsNormal antigen presentationImmune-privileged nicheIntestinal stem cellsMemory phenotypeImmune privilegeImmune escapeReporter miceAntigen presentationChronic infectionCytotoxic capacityEpithelial cellsNorovirus infectionStem cellsCell interactionsInfectionCell survivalEnteric microbesCells
2023
Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer
Coman M, Pusztai L, Hooley R, Andreveja L, Kim L, Joshi N, Bersenev A, Krause D, Park T. Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer. Journal Of Immunotherapy 2023, 47: 49-53. PMID: 37991241, DOI: 10.1097/cji.0000000000000495.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesCore needle biopsyTriple-negative breast cancerNeedle biopsyBreast cancerEx vivoT-cell receptor clonalityUltrasound-guided core needle biopsyTriple negative breast cancer tumorsMorbidity of surgeryAdoptive cell therapyBreast cancer tumorsTIL generationAdoptive transferTIL culturesMultiple lesionsCytokine secretionMetastatic cancerSame patientTumor tissueCell therapyPatientsCancer tumorsCancerSurgery1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. 1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma. 2023, a1133-a1133. DOI: 10.1136/jitc-2023-sitc2023.1025.Peer-Reviewed Original ResearchCancer- and infection-induced T cell exhaustion are distinct
Buck J, Joshi N. Cancer- and infection-induced T cell exhaustion are distinct. Nature Immunology 2023, 24: 1604-1605. PMID: 37709988, DOI: 10.1038/s41590-023-01624-9.Peer-Reviewed Original ResearchScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samplesPD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens
Damo M, Hornick N, Venkat A, William I, Clulo K, Venkatesan S, He J, Fagerberg E, Loza J, Kwok D, Tal A, Buck J, Cui C, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Joshi N. PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 2023, 619: 151-159. PMID: 37344588, PMCID: PMC10989189, DOI: 10.1038/s41586-023-06217-y.Peer-Reviewed Original ResearchConceptsEffector CD8 T cellsCD8 T cellsAntigen-specific effector CD8 T cellsAntigen-specific CD8 T cellsAntigen-expressing cellsT cell tolerancePD-1T cellsAdverse eventsCell toleranceCD8 T cell toleranceImmune-related adverse eventsPeripheral T cell repertoirePeripheral T cell toleranceNon-lesional skinT cell repertoireT-cell antigensPeripheral toleranceCheckpoint receptorsSkin biopsiesLocal infiltrationLocal pathologyCell repertoireMouse modelSkin toleranceT follicular helper cells in cancer, tertiary lymphoid structures, and beyond
Cui C, Craft J, Joshi N. T follicular helper cells in cancer, tertiary lymphoid structures, and beyond. Seminars In Immunology 2023, 69: 101797. PMID: 37343412, DOI: 10.1016/j.smim.2023.101797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor-associated tertiary lymphoid structuresFollicular helper cellsCD8 T cellsTertiary lymphoid structuresSecondary lymphoid organsT cellsHelper cellsLymphoid structuresImmune cellsB cellsCD4 T follicular helper cellsT Follicular Helper CellsTumor-infiltrating immune cellsCurrent immunotherapy regimensCheckpoint blockade immunotherapyCD4 T cellsImmune cell componentsLimited response rateFunctional immune cellsNovel therapeutic targetPotential therapeutic benefitT cell-B cell interactionsBlockade immunotherapyImmunotherapy regimensLymphoid organsMapping the gene space at single-cell resolution with gene signal pattern analysis
Venkat A, Damo M, Joshi N, Krishnaswamy S. Mapping the gene space at single-cell resolution with gene signal pattern analysis. The Journal Of Immunology 2023, 210: 251.03-251.03. DOI: 10.4049/jimmunol.210.supp.251.03.Peer-Reviewed Original ResearchGene-gene relationshipsGene spaceSingle-cell RNA sequencing analysisGene signalsSingle-cell resolutionRNA sequencing analysisMelanoma patient samplesScRNA-seq analysisTranscriptional programsCellular heterogeneityGene representationSequencing analysisCell typesSingle cellsPattern analysisCell subtypesCell subpopulationsMultiscale viewEffector functionsCellsMouse modelComputational methodsGenesCell spacePatient samples
2022
Novel Mouse Models for Cancer Immunology
Connolly K, Fitzgerald B, Damo M, Joshi N. Novel Mouse Models for Cancer Immunology. Annual Review Of Cancer Biology 2022, 6: 1-23. PMID: 36875867, PMCID: PMC9979244, DOI: 10.1146/annurev-cancerbio-070620-105523.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2021
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma
Fitzgerald B, Connolly KA, Cui C, Fagerberg E, Mariuzza DL, Hornick NI, Foster GG, William I, Cheung JF, Joshi NS. A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma. Cell Reports Methods 2021, 1: 100080. PMID: 34632444, PMCID: PMC8500377, DOI: 10.1016/j.crmeth.2021.100080.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaNeoantigen expressionTumor-specific CD8 T cellsCD8 T cellsImmune checkpoint therapyInfection-induced inflammationExpression of neoantigensCommon lung cancerLUAD cell linesCheckpoint therapyLung cancerTherapeutic responseT cellsImmune responseMouse modelCell responsesTumor inductionTumorsAdenocarcinomaCell linesNeoantigensKrasFuture studiesExpressionImmunotherapyA reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response
Connolly KA, Kuchroo M, Venkat A, Khatun A, Wang J, William I, Hornick NI, Fitzgerald BL, Damo M, Kasmani MY, Cui C, Fagerberg E, Monroy I, Hutchins A, Cheung JF, Foster GG, Mariuzza DL, Nader M, Zhao H, Cui W, Krishnaswamy S, Joshi NS. A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response. Science Immunology 2021, 6: eabg7836. PMID: 34597124, PMCID: PMC8593910, DOI: 10.1126/sciimmunol.abg7836.Peer-Reviewed Original ResearchConceptsTumor-specific CD8T cellsTumor microenvironmentOngoing anti-tumor immune responseChronic lymphocytic choriomeningitis virus (LCMV) infectionTumor-draining lymph nodesAnti-tumor immune responseLymphocytic choriomeningitis virus infectionIntratumoral T cellsEfficacy of immunotherapyT cell responsesTumor-draining lymphAntitumor T cellsT cell terminal differentiationStem-like CD8Immunologic shiftGene expression signaturesLymph nodesTerminal differentiationLung tumorsVirus infectionLung adenocarcinomaImmune responseCD8Cell responses
2020
Inducible de novo expression of neoantigens in tumor cells and mice
Damo M, Fitzgerald B, Lu Y, Nader M, William I, Cheung JF, Connolly KA, Foster GG, Akama-Garren E, Lee DY, Chang GP, Gocheva V, Schmidt LM, Boileve A, Wilson JH, Cui C, Monroy I, Gokare P, Cabeceiras P, Jacks T, Joshi NS. Inducible de novo expression of neoantigens in tumor cells and mice. Nature Biotechnology 2020, 39: 64-73. PMID: 32719479, PMCID: PMC7854852, DOI: 10.1038/s41587-020-0613-1.Peer-Reviewed Original ResearchConceptsT cell responsesLevel of regulationRNA splicingDNA recombinationGenetic regulationTolerance mechanismsInducible expressionNeoantigen expressionCell responsesNaïve T-cell responsesCD4 T cell responsesTumor cell linesPeripheral tolerance mechanismsT cell toleranceCentral T cell toleranceCell linesExpressionNovo expressionTight controlEndogenous CD8Antitumor immunityPeripheral toleranceAutoimmune diseasesT cellsThymus results
2018
The NINJA mouse: a novel model to study tissue-specific peripheral T cell tolerance
Damo M, Joshi N. The NINJA mouse: a novel model to study tissue-specific peripheral T cell tolerance. The Journal Of Immunology 2018, 200: 47.6-47.6. DOI: 10.4049/jimmunol.200.supp.47.6.Peer-Reviewed Original ResearchT-cell inhibitory pathwaysPeripheral T cell tolerancePeripheral toleranceT cell toleranceT cellsInhibitory pathwaysTissue-specific usageCell tolerancePersistent viral infectionNovel mouse modelAbsence of toleranceTissue-specific mechanismsT cell activationGenetic recombinationGp33-41LCMV epitopePathogenic autoimmunityPD-1Central toleranceNeoantigen expressionMouse modelAnimal modelsViral infectionChronic responsesImmunologic tools
2016
A Modular Assembly Platform for Rapid Generation of DNA Constructs
Akama-Garren EH, Joshi NS, Tammela T, Chang GP, Wagner BL, Lee DY, Rideout III W, Papagiannakopoulos T, Xue W, Jacks T. A Modular Assembly Platform for Rapid Generation of DNA Constructs. Scientific Reports 2016, 6: 16836. PMID: 26887506, PMCID: PMC4757859, DOI: 10.1038/srep16836.Peer-Reviewed Original ResearchConceptsAssembly platformDNA constructsInducible lentiviral systemCollection of promotersGeneration of knockTraditional cloning methodsGenetic screenRecombinant DNA technologyRNAi constructsGenomic elementsGenetic toolsSynthetic biologySynthetic promotersDNA fragmentsCloning methodGenetic componentDNA technologyTumor initiationLentiviral systemOne-step productionViral constructsPromoterRapid generationGMAPAssembly
2015
The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection
Dominguez C, Amezquita R, Guan T, Marshall H, Joshi N, Kleinstein S, Kaech S. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. Journal Of Cell Biology 2015, 211: 2113oia258. DOI: 10.1083/jcb.2113oia258.Peer-Reviewed Original ResearchRegulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses
Joshi NS, Akama-Garren EH, Lu Y, Lee DY, Chang GP, Li A, DuPage M, Tammela T, Kerper NR, Farago AF, Robbins R, Crowley DM, Bronson RT, Jacks T. Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses. Immunity 2015, 43: 579-590. PMID: 26341400, PMCID: PMC4826619, DOI: 10.1016/j.immuni.2015.08.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsCell ProliferationCells, CulturedDendritic CellsFlow CytometryForkhead Transcription FactorsImmunohistochemistryLuminescent ProteinsLung NeoplasmsLymphocyte ActivationLymphocyte DepletionLymphocytes, Tumor-InfiltratingMice, TransgenicMicroscopy, ConfocalNeoplasmsT-LymphocytesT-Lymphocytes, RegulatoryConceptsTreg cell functionDendritic cellsTreg cellsAnti-tumor T cell responsesTumor-associated tertiary lymphoid structuresEndogenous immune responseTreg cell depletionRegulatory T cellsAnti-tumor responseT cell responsesCell functionTertiary lymphoid structuresHuman lung cancerPoor patient prognosisLymphoid structuresCell depletionCancer patientsLung cancerPatient prognosisLung adenocarcinomaT cellsImmune responseMouse modelTherapeutic benefitTumor destruction
2007
Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor
Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, Gapin L, Kaech SM. Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor. Immunity 2007, 27: 281-295. PMID: 17723218, PMCID: PMC2034442, DOI: 10.1016/j.immuni.2007.07.010.Peer-Reviewed Original ResearchConceptsMemory precursor effector cellsEffector cellsT cellsIL-15Higher T-bet expressionT-bet transcription factorT cell primingT-bet expressionAmount of inflammationInnate immune systemMemory cell potentialEffector CD8T cell fateAcute infectionCell primingInflammatory cytokinesMemory precursorsT-betInterleukin-7IL-7R.Immune systemLow expressionLong-term maintenanceTranscription factorsHomeostatic turnover