2024
Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates
Jansen C, Pagadala M, Cardenas M, Prabhu R, Goyal S, Zhou C, Chappa P, Vo B, Ye C, Hopkins B, Zhong J, Klie A, Daniels T, Admassu M, Green I, Pfister N, Neill S, Switchenko J, Prokhnevska N, Hoang K, Torres M, Logan S, Olson J, Nduom E, del Balzo L, Patel K, Burri S, Asher A, Wilkinson S, Lake R, Kesarwala A, Higgins K, Patel P, Dhere V, Sowalsky A, Carter H, Khan M, Kissick H, Buchwald Z. Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates. Nature Communications 2024, 15: 8854. PMID: 39402027, PMCID: PMC11473782, DOI: 10.1038/s41467-024-53034-6.Peer-Reviewed Original ResearchConceptsPre-operative stereotactic radiosurgeryCD8 T cellsEffector-like cellsT cellsStereotactic radiosurgeryBrain metastasesCD8 T cell responsesEndpoint of overall survivalDistant brain failureResected brain metastasesEfficacy of immunotherapyT cell responsesAntigen presenting cellsSecondary clinical endpointsLocal recurrenceLeptomeningeal diseaseOverall survivalImmune compositionProspective trialsImmune nichePrimary endpointImmunological correlatesPresenting cellsClinical outcomesPilot studyAssociation of CD8 T cell infiltration in the tumor microenvironment with survival outcomes in patients with metastatic renal cell carcinoma (mRCC).
Goswamy R, Yildirim A, Wei M, Liu Y, Choi Y, Brown J, Nazha B, Master V, Martini D, Carthon B, Harris W, Kucuk O, Kissick H, Hartman C, McClintock G, Vo B, Jansen C, Zhuang T, Bilen M. Association of CD8 T cell infiltration in the tumor microenvironment with survival outcomes in patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: e16527-e16527. DOI: 10.1200/jco.2024.42.16_suppl.e16527.Peer-Reviewed Original ResearchCD8 T cell infiltrationMetastatic renal cell carcinomaProgression-free survivalT cell infiltrationCD8 T cellsCheckpoint inhibitorsOverall survivalTyrosine kinase inhibitorsT cellsSystemic therapyTumor microenvironmentMetastatic renal cell carcinoma patientsAssociated with favorable clinical outcomesProgression-free survival outcomesRetrospective analysis of patientsCombination checkpoint inhibitorsIntratumoral T cellsProgression free survivalImproved overall survivalFavorable clinical outcomesWinship Cancer InstituteKaplan Meier analysisAnalysis of patientsRenal cell carcinomaCox proportional hazards models
2023
Abstract B030: Form and function in intratumoral immune organization: Understanding the cellular composition of TCF1+ CD8+ T cell niches in human cancer
Jansen C, Vo B, Sobierajska E, Greenwald R, Mullane P, Prokhnevska N, Cardenas M, Bilen M, Osunkoya A, Master V, Kissick H. Abstract B030: Form and function in intratumoral immune organization: Understanding the cellular composition of TCF1+ CD8+ T cell niches in human cancer. Cancer Research 2023, 83: b030-b030. DOI: 10.1158/1538-7445.kidney23-b030.Peer-Reviewed Original ResearchTertiary lymphoid structuresSecondary lymphoid tissuesT cell responsesT cell zonesImmune nicheB cell zonesT cell nicheLymphoid tissueT cellsTumor tissuesEffective anti-tumor T cell responsesAnti-tumor T cell responsesDevelopment of T-cell functionStem-like CD8 T cellsImmune organsCD8 T cell activationCD8 T cell infiltrationTumor-infiltrating T cellsRobust T cell responsesCellular compositionB cell presenceHuman cancersAnti-tumor immunityResponse to immunotherapyCD8 T cellsStem-like CD4 T differentiation controls CD8 T cell immunity or tolerance in cancer
Cardenas M, Prokhnevska N, Jansen C, Sobierajska E, Master V, Kissick H. Stem-like CD4 T differentiation controls CD8 T cell immunity or tolerance in cancer. The Journal Of Immunology 2023, 210: 86.04-86.04. DOI: 10.4049/jimmunol.210.supp.86.04.Peer-Reviewed Original ResearchTumor-draining lymph nodesAnti-tumor responsesCD4 T cellsEffector differentiationT cellsT-cell anti-tumor responseTumor-specific CD4 T cellsCD8 T cell responsesCD8 T cell immunityT cell effector differentiationCD4 T cell differentiationReduced tumor burdenT cell responsesT cell immunityDraining lymph nodesT cell differentiationStem-like propertiesExpression of TCF1Tumor responseTumor burdenTreg differentiationLymph nodesCancer responseCD4 differentiationCD8
2022
CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor
Prokhnevska N, Cardenas M, Valanparambil R, Sobierajska E, Barwick B, Jansen C, Reyes Moon A, Gregorova P, delBalzo L, Greenwald R, Bilen M, Alemozaffar M, Joshi S, Cimmino C, Larsen C, Master V, Sanda M, Kissick H. CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor. Immunity 2022, 56: 107-124.e5. PMID: 36580918, PMCID: PMC10266440, DOI: 10.1016/j.immuni.2022.12.002.Peer-Reviewed Original ResearchConceptsTumor-draining lymph nodesCD8<sup>+</sup> T cell activationT cell activationCD8<sup>+</sup> T cellsStem-like cellsT cellsCell activationEffector differentiationLymph nodesTumor-specific CD8<sup>+</sup> T cellsActivated CD8<sup>+</sup> T cellsAnti-tumor T cell responsesTumor-draining lymph node cellsCD8+ T cell activationCo-stimulationT cell responsesAntigen-presenting cellsMurine tumor modelsResponse to cancerEffector phenotypeTumor immunotherapyTumor modelTumorCell responsesAcute viruses1033 Stem-like CD8 T-cells residing in antigen presenting immune niches are prognostic for local control in brain metastases and are sustained following radiation therapy
Jansen C, Chappa P, Prokhnevska N, Cardenas M, Prabhu R, Zhong J, Hoang K, Goyal S, Logan S, Olson J, Nduom E, Balzo L, Patel K, Burri S, Asher A, Wilkinson S, Lake R, Higgins K, Patel P, Dhere V, Torres M, Sowalsky A, Khan M, Kissick H, Buchwald Z. 1033 Stem-like CD8 T-cells residing in antigen presenting immune niches are prognostic for local control in brain metastases and are sustained following radiation therapy. 2022, a1075-a1075. DOI: 10.1136/jitc-2022-sitc2022.1033.Peer-Reviewed Original ResearchClinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood
Carlisle J, Jansen C, Cardenas M, Sobierajska E, Reyes A, Greenwald R, Del Balzo L, Prokhnevska N, Kucuk O, Carthon B, Mullane P, Osunkoya A, Baumgarten D, Hosseinzadeh F, Wilkinson S, Lake R, Sowalsky A, Liu Y, Master V, Bilen M, Kissick H. Clinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood. Journal For ImmunoTherapy Of Cancer 2022, 10: e004803. PMID: 35863822, PMCID: PMC9310235, DOI: 10.1136/jitc-2022-004803.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCD8 T cellsCheckpoint therapyT cellsHLA-DRCell carcinomaClinical benefitActivation markers HLA-DRAdvanced renal cell carcinomaPre-existing immune responsesImmune responsePredictor of clinical benefitPeripheral T cell activationPeripheral blood of patientsFlow cytometryT-cell receptor (TCR) sequencingIntratumoral T cellsAntitumor immune responseMarkers HLA-DRAbundant T cellsProportion of CD4Cornerstone of treatmentT cell activationBlood of patientsPredicting therapeutic responseCD8 T cell activation in cancer is comprised of two distinct phases
Prokhnevska N, Cardenas M, Valanparambil R, Sobierajska E, Jansen C, Master V, Sanda M, Kissick H. CD8 T cell activation in cancer is comprised of two distinct phases. The Journal Of Immunology 2022, 208: 121.09-121.09. DOI: 10.4049/jimmunol.208.supp.121.09.Peer-Reviewed Original ResearchStem-like CD8 T cellsCD8 T cellsTumor-draining LNCD8 T cell activationT cellsT cell activationCo-stimulationLCMV-GPTumor-specific CD8 T cellsT cell responses to tumorsHeterogeneous T-cell subsetsCD8 T cell differentiationAutologous dendritic cellsProstate cancer modelResponse to tumorsT cell subsetsAntigen presenting cellsCo-stimulatory signalsTumor-bearing miceT cell differentiationStem-like phenotypeDifferentiation ex vivoCD8 responsesEffector phenotypeDendritic cells
2021
Case Report: Exceptional Response to Nivolumab Plus Ipilimumab in a Young Woman With TFE3-SFPQ Fusion Translocation-Associated Renal Cell Carcinoma
Martini D, Jansen C, Harik L, Evans S, Olsen T, Master V, Kissick H, Bilen M. Case Report: Exceptional Response to Nivolumab Plus Ipilimumab in a Young Woman With TFE3-SFPQ Fusion Translocation-Associated Renal Cell Carcinoma. Frontiers In Oncology 2021, 11: 793808. PMID: 34976834, PMCID: PMC8716393, DOI: 10.3389/fonc.2021.793808.Peer-Reviewed Original ResearchCD8+ T cellsResponse to treatmentT cellsLymphovascular invasionTranslocation-associated renal cell carcinomaFoci of lymphovascular invasionBiomarker of response to treatmentRadiographic response to treatmentFirst-line treatment optionFavorable response to treatmentIntratumoral immune infiltrationImmune checkpoint inhibitorsResponse to nivolumabRenal cell carcinomaPrimary tumor samplesYear old femalePresence of lymphocytesCheckpoint inhibitorsProgression-freeRare malignancyCell carcinomaPredictive biomarkersImmune infiltrationAggressive malignancyTreatment options640 Stem-like CD4 T cells in cancer
Cardenas M, Prokhnevska N, Jansen C, Master V, Kissick H. 640 Stem-like CD4 T cells in cancer. Journal For ImmunoTherapy Of Cancer 2021, 9: a669-a669. DOI: 10.1136/jitc-2021-sitc2021.640.Peer-Reviewed Original ResearchCD4 T cellsAnti-tumor responsesT cellsTh1-likeEffector subsetsEffector lineagesTumor-infiltrating CD4 T cellsVirus-specific CD4 T cellsInfiltrating CD4 T cellsResponses to tumor antigensFlow cytometryEx vivo functional analysisProstate cancer mouse modelCancer mouse modelGenes associated with stemnessEmory University HospitalPlasticity in vitroKidney cancer patientsHypothesis in vivoLCMV glycoproteinCD4 subsetTfh cellsTreg cellsEffector populationsTumor antigens658 CD8 T cell activation in cancer is comprised of two distinct phases
Prokhnevska N, Cardenas M, Valanparambil R, Sobierajska E, Jansen C, Master V, Sanda M, Kissick H. 658 CD8 T cell activation in cancer is comprised of two distinct phases. Journal For ImmunoTherapy Of Cancer 2021, 9: a686-a686. DOI: 10.1136/jitc-2021-sitc2021.658.Peer-Reviewed Original ResearchTumor-draining lymph nodesCD8 T cell activationCD8 T cellsStem-like CD8 T cellsT cell activationResponse to tumorsT cellsCo-stimulationEffector programTumor-specific CD8 T cellsImmune response to tumorsSubsets of CD8 T cellsModel of T cell differentiationActivated CD8 T cellsProstate cancer mouse modelCD8 T cell biologyCancer mouse modelAntigen presenting cellsT cell differentiationT cell biologyStem-like cellsAutologous tumorCD8 infiltrationCD8 subsetsEffector phenotypeA Subset of Localized Prostate Cancer Displays an Immunogenic Phenotype Associated with Losses of Key Tumor Suppressor Genes
Calagua C, Ficial M, Jansen C, Hirz T, Del Balzo L, Wilkinson S, Lake R, Ku A, Voznesensky O, Sykes D, Saylor P, Ye H, Signoretti S, Kissick H, Sowalsky A, Balk S, Einstein D. A Subset of Localized Prostate Cancer Displays an Immunogenic Phenotype Associated with Losses of Key Tumor Suppressor Genes. Clinical Cancer Research 2021, 27: 4836-4847. PMID: 34168052, PMCID: PMC8416924, DOI: 10.1158/1078-0432.ccr-21-0121.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCD8<sup>+</sup> T cellsImmune checkpoint inhibitorsPD-L1 expressionLocalized prostate cancerPrimary prostate cancerProstate cancerT cellsPD-L1Density of CD8<sup>+</sup> T cellsHigh-risk primary prostate cancerCD8 T-cell densityCharacterized tumor infiltrating lymphocytesLocalized prostate cancer casesPD-1<sup>+</sup> cellsTumor PD-L1 expressionUnique tumor immune microenvironmentPD-1 expressionTumor-infiltrating lymphocytesT-cell densityCD8 T cellsTumor immune microenvironmentTumor mutational burdenProstate cancer casesT-cell contentCD8 T cell differentiation in cancer is comprised of two distinct phases
Prokhnevska N, Cardenas M, Valanparambil R, Jansen C, Master V, Sanda M, Kissick H. CD8 T cell differentiation in cancer is comprised of two distinct phases. The Journal Of Immunology 2021, 206: 57.04-57.04. DOI: 10.4049/jimmunol.206.supp.57.04.Peer-Reviewed Original ResearchTumor-specific CD8 T cellsTumor-draining lymph nodesCD8 T cellsCD8 T cell differentiationResponse to tumorsT cellsT cell differentiationStem-like CD8 T cellsT cell responses to tumorsUndifferentiated phenotypeImmune response to tumorsSubsets of CD8 T cellsCD8 T cell subsetsImmune response to cancerTumor-specific antigensProstate cancer modelT cell subsetsHuman prostate cancerDraining lymph nodesResponse to cancerCD8 infiltrationLCMV glycoproteinProstate cancerLymph nodesCD8Abstract PO-041: An immunologic niche of antigen presenting cells and stem-like CD8+ T-cells is present in non-small cell lung cancer brain metastases
Jansen C, del Balzo L, Prabhu R, Logan S, Chappa P, Patel K, Wilkinson S, Lake R, Shu H, Zhong J, Dhere V, Olson J, Sowalsky A, Khan M, Kissick H, Buchwald Z. Abstract PO-041: An immunologic niche of antigen presenting cells and stem-like CD8+ T-cells is present in non-small cell lung cancer brain metastases. Clinical Cancer Research 2021, 27: po-041-po-041. DOI: 10.1158/1557-3265.radsci21-po-041.Peer-Reviewed Original ResearchCD8+ T cellsStem-like CD8+ T cellsNon-small cell lung cancer brain metastasisNon-small cell lung cancerAntigen presenting cellsLung cancer brain metastasisStereotactic radiosurgeryBrain metastasesCancer brain metastasesImmune nicheT cellsPresenting cellsMHC-II+TCF-1CD8+ T cell infiltrationImmunological nichePost-operative stereotactic radiosurgeryPre-operative stereotactic radiosurgeryT cell infiltrationCell lung cancerCohort of patientsCheckpoint blockadePD-1Disease recurrenceGenitourinary malignancies
2020
CD4 T cell phenotypes differentially modulate the CD8 T cell response in kidney cancer
Cardenas M, Prokhnevska N, Jansen C, Master V, Kissick H. CD4 T cell phenotypes differentially modulate the CD8 T cell response in kidney cancer. The Journal Of Immunology 2020, 204: 165.1-165.1. DOI: 10.4049/jimmunol.204.supp.165.1.Peer-Reviewed Original ResearchTumor-infiltrating CD4 T cellsInfiltrating CD4 T cellsCD8 T cell responsesCD4 T cellsAnti-tumor responsesT cell responsesCD8 T cell infiltrationT cellsKidney cancer patientsTumor-specific CD8 T-cell responsesTumor-infiltrating CD8 T cellsSubsets of CD4 T cellsCancer patientsCD8 T cell functionMaster transcription factor Foxp3CD8 T cell differentiationCD4 T cell phenotypeRenal cell carcinoma patientsResponse to immunotherapyCD8 T cellsT cell infiltrationT regulatory cellsT-cell phenotypeCell carcinoma patientsTranscription factor Foxp3Tumor-specific CD8 T cell activation in draining lymph nodes supports the anti-tumor CD8 T cell response
Prokhnevska N, Cardenas M, Jansen C, Valanparambil R, Master V, Sanda M, Kissick H. Tumor-specific CD8 T cell activation in draining lymph nodes supports the anti-tumor CD8 T cell response. The Journal Of Immunology 2020, 204: 165.5-165.5. DOI: 10.4049/jimmunol.204.supp.165.5.Peer-Reviewed Original ResearchTumor-specific CD8 T cellsCD8 T cellsStem-like CD8 T cellsCD8 T cell activationT cellsT cell activationEffector programLymph nodesCD8 T cell responsesImmune response to tumorsTumor-draining lymph nodesCD8 T cell infiltrationSubsets of CD8 T cellsAnti-tumor responsesT cell infiltrationResponse to tumorsTumor-specific antigensProstate cancer modelT cell responsesDraining lymph nodesAcute viral infectionT cell immunologyCD8 responsesLCMV glycoproteinCD62L expression
2019
An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
Jansen C, Prokhnevska N, Master V, Sanda M, Carlisle J, Bilen M, Cardenas M, Wilkinson S, Lake R, Sowalsky A, Valanparambil R, Hudson W, McGuire D, Melnick K, Khan A, Kim K, Chang Y, Kim A, Filson C, Alemozaffar M, Osunkoya A, Mullane P, Ellis C, Akondy R, Im S, Kamphorst A, Reyes A, Liu Y, Kissick H. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature 2019, 576: 465-470. PMID: 31827286, PMCID: PMC7108171, DOI: 10.1038/s41586-019-1836-5.Peer-Reviewed Original ResearchConceptsCD8 T cellsStem-like CD8 T cellsT cellsStem-like T cellsCD8 T cell infiltrationCD8 T cell responsesMechanism of immune escapeTumor-infiltrating lymphocytesT cell infiltrationT cell responsesStem-like cellsSurvival benefitImmune nicheProgressive diseaseImmune escapeTumor typesTumorCD8Human cancersDifferentiation processLymphocytesPatientsCancerInfiltrationSurvivalAbstract 2700: CD8 T-cell infiltration into renal tumors requires a supportive antigen-presenting niche
Jansen C, Prokhnevska N, Master V, Carlisle J, Bilen M, Reyes A, Kissick H. Abstract 2700: CD8 T-cell infiltration into renal tumors requires a supportive antigen-presenting niche. Cancer Research 2019, 79: 2700-2700. DOI: 10.1158/1538-7445.am2019-2700.Peer-Reviewed Original ResearchCD8 T cell infiltrationT cell infiltrationTumor-infiltrating lymphocytesT cell responsesRenal cell carcinomaStem-like T cellsCancer-specific survivalT cellsRenal tumorsPatient survivalCD8 tumor-infiltrating lymphocytesPoor T-cell infiltrationDisease progressionAnti-tumor immune responseCD8 T cell responsesImmune responseTumor-infiltrating immune cellsFlow cytometryRenal cell carcinoma patientsCD8 T cellsStage III patientsIntensification of therapyRenal cell tumorsFollow-up timeEmory University Hospital