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 studyCirculating Tumor DNA in Genitourinary Cancers: Detection, Prognostics, and Therapeutic Implications
Gerke M, Jansen C, Bilen M. Circulating Tumor DNA in Genitourinary Cancers: Detection, Prognostics, and Therapeutic Implications. Cancers 2024, 16: 2280. PMID: 38927984, PMCID: PMC11201475, DOI: 10.3390/cancers16122280.Peer-Reviewed Original ResearchRenal cell carcinomaGU cancersProstate cancerBladder cancerGenitourinary (GU) cancersUtilization of liquid biopsyCastration-resistant prostate cancerDetect residual diseaseCirculating tumor DNATherapeutic response predictionCtDNA assaysResidual diseaseCtDNA analysisCell carcinomaTumor DNAGenitourinary cancersPrognostic informationClinical detection methodsTreatment responseGenomic alterationsLiquid biopsyClinical trialsTherapeutic implicationsCancerCtDNAAssociation 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 modelsUnderstanding and overcoming resistance to immunotherapy in genitourinary cancers
Evans S, Jani Y, Jansen C, Yildirim A, Kalemoglu E, Bilen M. Understanding and overcoming resistance to immunotherapy in genitourinary cancers. Cancer Biology & Therapy 2024, 25: 2342599. PMID: 38629578, PMCID: PMC11028033, DOI: 10.1080/15384047.2024.2342599.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsResistance to immunotherapyImmunotherapy resistanceTargeted therapyGenitourinary (GU) cancersCombined immune checkpoint inhibitorsIntroduction of novel immunotherapiesMechanisms of immunotherapy resistanceOvercome resistance to immunotherapyCancer cellsHost immune profileResponse to immunotherapyNovel targeted therapiesImmune system's rolePredictors of responseAttack cancer cellsImmune system's abilityStandard of careCheckpoint inhibitorsSequential therapyNovel immunotherapiesCombination therapyTreatment failureGU cancersTreatment landscapeImpact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis
Patel J, Woo Y, Draper A, Jansen C, Carlisle J, Innominato P, Lévi F, Dhabaan L, Master V, Bilen M, Khan M, Lowe M, Kissick H, Buchwald Z, Qian D. Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis. Journal For ImmunoTherapy Of Cancer 2024, 12: e008011. PMID: 38531662, PMCID: PMC10966813, DOI: 10.1136/jitc-2023-008011.Peer-Reviewed Original ResearchConceptsInfusions of immune checkpoint inhibitorsMetastatic renal cell carcinomaProgression-free survivalOverall survivalRenal cell carcinomaCell carcinomaInternational Metastatic RCC Database Consortium risk scoreAssociated with longer progression-free survivalLung cancerGroup BGroup ATime of ICI initiationLonger progression-free survivalNon-small cell lung cancerMultivariable Cox proportional hazards regressionImmune checkpoint inhibitorsPretreatment lactate dehydrogenaseCell lung cancerCox proportional hazards regressionAdaptive immune responsesProportional hazards regressionMulticenter cohort analysisCheckpoint inhibitorsICI initiationMetastatic melanomaHow to diversify the dwindling physician–scientist workforce after the US affirmative action ban
Ding J, Christophers B, Rupert D, Tang C, Serafini R, Jansen C, Curtis M, Chesebro A, Waldman A. How to diversify the dwindling physician–scientist workforce after the US affirmative action ban. Nature Medicine 2024, 30: 635-637. PMID: 38291299, DOI: 10.1038/s41591-023-02787-6.Peer-Reviewed Original ResearchEstablished and Emerging Biomarkers of Immunotherapy in Renal Cell Carcinoma
Jani Y, Jansen C, Gerke M, Bilen M. Established and Emerging Biomarkers of Immunotherapy in Renal Cell Carcinoma. Immunotherapy 2024, 16: 405-426. PMID: 38264827, DOI: 10.2217/imt-2023-0267.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCell carcinomaImmune checkpoint inhibitorsBiomarker of immunotherapyRisk of adverse eventsSignificant side effectsCheckpoint inhibitorsDevelopment of biomarkersAdverse eventsImmunotherapyTherapeutic efficacySide effectsPatientsClinical biomarkersPatient's diseaseTherapeutic biomarkersClinician's abilityBiomarkersCarcinomaPatient careImproving clinicians' abilityEfficacyThe Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers
Mustafa S, Jansen C, Jani Y, Evans S, Zhuang T, Brown J, Nazha B, Master V, Bilen M. The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers. Biomarker Insights 2024, 19: 11772719241254179. PMID: 38827239, PMCID: PMC11143877, DOI: 10.1177/11772719241254179.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsResponse to immunotherapyAdverse eventsTreatment of genitourinary malignanciesImmune checkpoint blockadeSelection of therapySignificant side effectsCheckpoint blockadeCheckpoint inhibitorsGU malignanciesGenitourinary malignanciesPatient tumorsTreatment landscapeReview of biomarkersGenitourinary cancersGU tumorsPreclinical studiesPrognostic toolSide effectsTherapyBiomarker developmentTumorPatientsImmunotherapy
2023
Cutaneous T-cell lymphoma with CNS involvement: a case series and review of the literature
Preston J, Jansen C, Kosaraju S, Niyogusaba T, Zhuang T, Iwamoto S, Hutto S, Lechowicz M, Allen P. Cutaneous T-cell lymphoma with CNS involvement: a case series and review of the literature. CNS Oncology 2023, 12: cns105. PMID: 37877303, PMCID: PMC10701703, DOI: 10.2217/cns-2023-0014.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaT-cell lymphomaCentral nervous systemCNS metastasesCases of cutaneous T-cell lymphomaDevelopment of CNS metastasesCentral nervous system involvementRare hematologic malignancyCNS-directed therapyDegree of remissionHematologic malignanciesProgressive diseaseMedian timeCase seriesTreatment responseTherapeutic guidelinesPathological characteristicsCutaneous lesionsMetastasisNervous systemLymphomaPatientsSurvivalInvolvementRemissionPhysician–scientist trainees with parenting responsibilities need financial and childcare support
Jansen C, Sugiura A, Stalbow L, Nguyen C, Lever J, Peiper A, Plaza-Jennings A, Varvel L, Williams M, Zarrinpar A, Swartz T. Physician–scientist trainees with parenting responsibilities need financial and childcare support. Nature Medicine 2023, 29: 2990-2992. PMID: 37853137, PMCID: PMC10842773, DOI: 10.1038/s41591-023-02606-y.Peer-Reviewed Original ResearchCase Report: Exceptional response to nivolumab plus cabozantinib in a patient with extrarenal clear cell renal cell carcinoma
Jansen C, Choi Y, Evans S, Greenwald R, Behnke J, Hartman C, Kissick H, Harik L, Bilen M. Case Report: Exceptional response to nivolumab plus cabozantinib in a patient with extrarenal clear cell renal cell carcinoma. Frontiers In Oncology 2023, 13: 1271255. PMID: 37860195, PMCID: PMC10582703, DOI: 10.3389/fonc.2023.1271255.Peer-Reviewed Original ResearchClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaSystemic therapyCell carcinomaTyrosine kinase inhibitor-targeted therapyResponse to systemic therapyWell-tolerated treatment optionCD8+T cell infiltrationCombination of immunotherapyResponse to nivolumabImmunotherapy to patientsMinimal adverse effectsVEGF-TKIDisease recurrenceCombination therapyTherapeutic regimensTherapeutic responseConsensus guidelinesTreatment optionsOptimal treatmentTumor tissuesRare typePatientsTherapyAbstract B009: Isolating human RCC tumor cells details evolutionary relationships between cancer cell subsets and a role of OXPHOS in disease progression
Sobierajska E, Medina C, Gregorova P, Vo B, Greenwald R, Jansen C, Larsen C, Master V, Kissick H. Abstract B009: Isolating human RCC tumor cells details evolutionary relationships between cancer cell subsets and a role of OXPHOS in disease progression. Cancer Research 2023, 83: b009-b009. DOI: 10.1158/1538-7445.kidney23-b009.Peer-Reviewed Original ResearchOxidative phosphorylationEvolutionary relationshipsRNA-seqCancer cellsCancer cell subsetsRCC tumor cellsWhole-genome sequencingMutation detection sensitivityDisease progressionUnique to cancer cellsKidney cancer cellsCell differentiation pathsIncreased oxidative phosphorylationCell subsetsEpithelial to mesenchymal transitionGenome sequenceIncreased proliferative stateTumor cellsTumor tissuesScRNA-seqOxidative metabolismAssociated with disease recurrenceCD8 T cell numbersMitochondrial potentialMitochondrial fitnessAbstract 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 antigens