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 ResearchMeSH KeywordsAdenocarcinomaAnimalsB-LymphocytesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorHumansInterleukinsLung NeoplasmsMiceMice, Inbred C57BLMice, KnockoutConceptsCD8 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 ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesFemaleImmunotherapyLung NeoplasmsLymph NodesLymphocyte ActivationMaleMiceMice, Inbred C57BLTumor MicroenvironmentConceptsTumor-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 ResearchMeSH KeywordsAnimalsAntigens, NeoplasmCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell EngineeringFemaleHumansMiceOrgan SpecificityRNA SplicingTumor Cells, CulturedConceptsT 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
2019
Stereotactic Body Radiation and Interleukin-12 Combination Therapy Eradicates Pancreatic Tumors by Repolarizing the Immune Microenvironment
Mills B, Connolly K, Ye J, Murphy J, Uccello T, Han B, Zhao T, Drage M, Murthy A, Qiu H, Patel A, Figueroa N, Johnston C, Prieto P, Egilmez N, Belt B, Lord E, Linehan D, Gerber S. Stereotactic Body Radiation and Interleukin-12 Combination Therapy Eradicates Pancreatic Tumors by Repolarizing the Immune Microenvironment. Cell Reports 2019, 29: 406-421.e5. PMID: 31597100, PMCID: PMC6919969, DOI: 10.1016/j.celrep.2019.08.095.Peer-Reviewed Original ResearchConceptsStereotactic body radiation therapyMultiple preclinical mouse modelsPancreatic ductal adenocarcinoma patientsEffective neoadjuvant therapyAdvanced metastatic diseaseStereotactic body radiationDuctal adenocarcinoma patientsLate-stage diseaseInterferon-gamma productionBody radiation therapySystemic tumor immunityPreclinical mouse modelsNeoadjuvant approachNeoadjuvant therapyLiver metastasesMetastatic diseaseCD8 TTumor immunityAdenocarcinoma patientsImmune microenvironmentTumor reductionMS administrationTherapy resultsPancreatic tumorsGamma production
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