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 efforts
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
Investigating Tumor-Associated Tertiary Lymphoid Structures in Murine Lung Adenocarcinoma
Connolly KA, Nader M, Joshi N. Investigating Tumor-Associated Tertiary Lymphoid Structures in Murine Lung Adenocarcinoma. Methods In Molecular Biology 2018, 1845: 259-273. PMID: 30141018, DOI: 10.1007/978-1-4939-8709-2_15.ChaptersConceptsTertiary lymphoid structuresLung adenocarcinomaLymphoid structuresImmune cellsFluorescence-activated cell sortingLung lobesTumor-associated tertiary lymphoid structuresHuman lung cancer patientsStrong antitumor immune responseAdvanced stage diseaseAntitumor immune responseRegulatory T cellsLung cancer patientsMurine lung adenocarcinomaFunctional immune systemAnimal tumor modelsLymph nodesCancer patientsAutochthonous tumorsT cellsImmune responseMouse modelTherapeutic interventionsImmune systemTumor growth
2016
Increasing the efficacy of radiotherapy by modulating the CCR2/CCR5 chemokine axes
Connolly K, Belt B, Figueroa N, Murthy A, Patel A, Kim M, Lord E, Linehan D, Gerber S. Increasing the efficacy of radiotherapy by modulating the CCR2/CCR5 chemokine axes. Oncotarget 2016, 5: 86522-86535. PMID: 27852031, PMCID: PMC5349932, DOI: 10.18632/oncotarget.13287.Peer-Reviewed Original ResearchConceptsEfficacy of radiotherapyImmune responseSyngeneic tumor cell linesCancer typesIntratumoral immune infiltrateAnti-tumor immunityIntratumoral immune responseEffect of radiotherapyMechanism of radiotherapyEffectiveness of radiotherapyChemokine axesRadioresponsive tumorsLocal radiotherapyImmunosuppressive cellsImmune infiltratesRT failureTumor recurrenceImmune cellsCCR5 antagonistsMurine modelHigh incidenceRadiotherapyTumor growthRT efficacyTumor site
2013
Radio‐responsive tumors exhibit greater intratumoral immune activity than nonresponsive tumors
Gerber S, Lim J, Connolly K, Sedlacek A, Barlow M, Murphy S, Egilmez N, Lord E. Radio‐responsive tumors exhibit greater intratumoral immune activity than nonresponsive tumors. International Journal Of Cancer 2013, 134: 2383-2392. PMID: 24154990, PMCID: PMC3949198, DOI: 10.1002/ijc.28558.Peer-Reviewed Original ResearchConceptsRadiation therapyIL-12Immune cellsImmune responseEffectiveness of RTEfficacy of RTCD8 T cellsIntratumoral immune cellsCytokines IL-12Effectiveness of therapyOutcome of radiotherapyEfficacy of treatmentComplete remissionResponsive tumorsCure rateNonresponsive tumorsT cellsImmune activityAntitumor effectsImmune systemCombinatorial treatmentTumor modelColon adenocarcinomaNonrespondersTumors