2024
Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma
Lu B, Lucca L, Lewis W, Wang J, Nogueira C, Heer S, Rayon-Estrada V, Axisa P, Reeves S, Buitrago-Pocasangre N, Pham G, Kojima M, Wei W, Aizenbud L, Bacchiocchi A, Zhang L, Walewski J, Chiang V, Olino K, Clune J, Halaban R, Kluger Y, Coyle A, Kisielow J, Obermair F, Kluger H, Hafler D. Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma. Nature Immunology 2024, 1-10. PMID: 39609626, DOI: 10.1038/s41590-024-02023-4.Peer-Reviewed Original ResearchCD8+ T cellsAnti-tumor immunityRegulatory T cellsT cellsSubpopulation of CD8+ T cellsCytotoxic CD8+ T cellsHuman CD8+ T cellsTumor antigen-specific CD8Impaired anti-tumor immunityTumor antigen-specificPoor overall survivalTumor rejectionKIR expressionOverall survivalTumor antigensImmune evasionCellular mediatorsHuman cancersCD8MelanomaTumorTranscriptional programsFunctional heterogeneityImmunityPatients1102P Immune checkpoint inhibitor rechallenge after treatment with tumor-infiltrating lymphocytes in unresectable melanoma
Warner A, Smithy J, Los C, Kalvin H, Hasson N, Amaria R, Czapla J, Schollenberger M, furness A, Hassel J, Wermke M, Gallegos J, Lutzky J, Lipson E, Sullivan R, Kluger H, Panageas K, Klobuch S, Haanen J, Shoushtari A. 1102P Immune checkpoint inhibitor rechallenge after treatment with tumor-infiltrating lymphocytes in unresectable melanoma. Annals Of Oncology 2024, 35: s730-s731. DOI: 10.1016/j.annonc.2024.08.1170.Peer-Reviewed Original ResearchGP100 expression is variable in intensity in melanoma
Mann J, Hasson N, Su D, Adeniran A, Smalley K, Djureinovic D, Jilaveanu L, Schoenfeld D, Kluger H. GP100 expression is variable in intensity in melanoma. Cancer Immunology, Immunotherapy 2024, 73: 191. PMID: 39105816, PMCID: PMC11303354, DOI: 10.1007/s00262-024-03776-5.Peer-Reviewed Original ResearchConceptsGp100 expressionCutaneous melanomaTreatment of cutaneous melanomaAdvanced cutaneous melanomaT-cell engagersImprove patient selectionMetastatic melanomaUveal melanomaMetastatic samplesPatient selectionClinical trialsMelanomaQuantitative immunofluorescence methodGp100Improve outcomesImmunofluorescence methodTherapeutic intentDrugCellular productsExpressionTebentafuspImmunohistochemistryCauses of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era
Lee D, McNamara M, Yang A, Yaskolko M, Kluger H, Tran T, Olino K, Clune J, Sznol M, Ishizuka J. Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era. Pigment Cell & Melanoma Research 2024, 37: 847-853. PMID: 39073002, DOI: 10.1111/pcmr.13188.Peer-Reviewed Original ResearchSite of metastasisPattern of metastatic diseaseMelanoma mortalityRetrospective observational cohort studyCause of cancer mortalityDistant lymph nodesObservational cohort studyDiagnosis to deathImmunotherapy eraAdvanced melanomaMetastatic diagnosisMetastatic diseaseMetastatic melanomaImmunotherapy treatmentRespiratory failureCause of deathMedian timeLymph nodesTherapeutic advancesCohort studyMelanomaImmunotherapyMechanism of deathPatientsEnd of lifeSpatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.
Aung T, Warrell J, Martinez-Morilla S, Gavrielatou N, Vathiotis I, Yaghoobi V, Kluger H, Gerstein M, Rimm D. Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma. Clinical Cancer Research 2024, 30: 3520-3532. PMID: 38837895, PMCID: PMC11326985, DOI: 10.1158/1078-0432.ccr-23-3932.Peer-Reviewed Original ResearchGene signatureResistance to immunotherapyResponse to immunotherapyPrediction of treatment outcomeResistant to treatmentAccurate prediction of treatment outcomePredictive of responseImmunotherapy outcomesMelanoma patientsMelanoma specimensValidation cohortPatient stratificationDiscovery cohortTreatment outcomesImmunotherapyMelanomaTumorPatientsCohortS100BOutcomesGene expression dataGenesCD68+macrophagesExpression dataVascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumor
2023
119O Long-term efficacy and patterns of response of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: A 4-year analysis of the C-144-01 study
Medina T, Chesney J, Whitman E, Kluger H, Thomas S, Sarnaik A, Kirkwood J, Larkin J, Weber J, Hamid O, Wermke M, Finckenstein F, Chou J, Gastman B, Sulur G, Wu X, Shi W, Domingo-Musibay E. 119O Long-term efficacy and patterns of response of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: A 4-year analysis of the C-144-01 study. Immuno-Oncology Technology 2023, 20: 100591. DOI: 10.1016/j.iotech.2023.100591.Peer-Reviewed Original Research1025 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 Research830 Inhibition of macrophage migration inhibitory factor (MIF) to overcome immune checkpoint resistance in melanoma
Sanchez-Zuno G, Caulfield J, Leng L, Zhang L, Jilaveanu L, Kluger H, Bucala R, Tran T. 830 Inhibition of macrophage migration inhibitory factor (MIF) to overcome immune checkpoint resistance in melanoma. 2023, a928-a928. DOI: 10.1136/jitc-2023-sitc2023.0830.Peer-Reviewed Original Research776 Long-term efficacy and safety of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: a 4-year analysis of the C-144–01 study
Medina T, Chesney J, Whitman E, Kluger H, Thomas S, Sarnaik A, Kirkwood J, Larkin J, Weber J, Hamid O, Wermke M, Finckenstein F, Chou J, Gastman B, Sulur G, Wu X, Shi W, Domingo-Musibay E. 776 Long-term efficacy and safety of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: a 4-year analysis of the C-144–01 study. 2023, a873-a873. DOI: 10.1136/jitc-2023-sitc2023.0776.Peer-Reviewed Original Research1086MO Lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced mucosal melanoma after progression on immune checkpoint inhibitors (ICI): Results from the phase II C-144-01 study
Grigoleit G, Kluger H, Thomas S, Chesney J, Domingo-Musibay E, Sanmamed M, Medina T, Ziemer M, Whitman E, Finckenstein F, Chou J, Wu X, Sulur G, Shi W, Sarnaik A. 1086MO Lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced mucosal melanoma after progression on immune checkpoint inhibitors (ICI): Results from the phase II C-144-01 study. Annals Of Oncology 2023, 34: s654. DOI: 10.1016/j.annonc.2023.09.2220.Peer-Reviewed Original ResearchLeptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care
Smalley I, Boire A, Brastianos P, Kluger H, Hernando‐Monge E, Forsyth P, Ahmed K, Smalley K, Ferguson S, Davies M, Oliva I. Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care. Pigment Cell & Melanoma Research 2023, 37: 51-67. PMID: 37622466, DOI: 10.1111/pcmr.13116.Peer-Reviewed Original ResearchCheckMate-915: does adjuvant CTLA-4 blockade play a role in resected melanoma?
Su D, Kluger H, Weiss S. CheckMate-915: does adjuvant CTLA-4 blockade play a role in resected melanoma? Annals Of Translational Medicine 2023, 0: 0-0. PMID: 37675335, PMCID: PMC10477634, DOI: 10.21037/atm-23-754.Peer-Reviewed Original Research290 Response to Lifileucel Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy after ICI Resistance Regardless of Definition: An Analysis of the C-144-01 Trial in Patients with Advanced Melanoma
Sarnaik A, Chesney J, Medina T, Hamid O, Thomas S, Wermke M, Gontcharova V, Damirchi B, Dean J, Mastellar E, Wu X, Shi W, Kluger H. 290 Response to Lifileucel Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy after ICI Resistance Regardless of Definition: An Analysis of the C-144-01 Trial in Patients with Advanced Melanoma. Transplantation And Cellular Therapy 2023, 29: s223-s224. DOI: 10.1016/s2666-6367(23)00359-7.Peer-Reviewed Original ResearchMelanoma in pregnancy
Czeyda-Pommersheim F, Kluger H, Langdon J, Menias C, VanBuren W, Leventhal J, Baumann R, Revzin M. Melanoma in pregnancy. Abdominal Radiology 2023, 48: 1740-1751. PMID: 36719425, DOI: 10.1007/s00261-022-03796-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2022
35MO Number of IL-2 doses and clinical outcomes of tumor-infiltrating lymphocyte (TIL) cell therapy: Post hoc analysis of the C-144-01 trial of lifileucel in patients with advanced melanoma
Hassel J, Sarnaik A, Chesney J, Medina T, Hamid O, Thomas S, Wermke M, Domingo-Musibay E, Kirkwood J, Larkin J, Weber J, Fernandez A, Rodriguez J, Thomas I, Corrie P, Gontcharova V, Wu X, Shi W, Kluger H. 35MO Number of IL-2 doses and clinical outcomes of tumor-infiltrating lymphocyte (TIL) cell therapy: Post hoc analysis of the C-144-01 trial of lifileucel in patients with advanced melanoma. Immuno-Oncology Technology 2022, 16: 100140. DOI: 10.1016/j.iotech.2022.100140.Peer-Reviewed Original ResearchUnilateral Pneumonitis and Hydropneumothorax Following Pembrolizumab
Sanchez A, Kahn P, Minerowicz C, Kluger H. Unilateral Pneumonitis and Hydropneumothorax Following Pembrolizumab. Journal Of Brown Hospital Medicine 2022, 2 DOI: 10.56305/001c.39747.Peer-Reviewed Case Reports and Technical NotesCheckpoint inhibitor pneumonitisTransbronchial biopsy resultsBronchoalveolar lavage fluidProgressive dyspneaDry coughPembrolizumab monotherapyLavage fluidRadiographic findingsBiopsy resultsMetastatic melanomaPleural fluidPneumonitisHydropneumothoraxPembrolizumabDyspneaMonotherapyCoughPneumoniaMelanomaSymptomsInfectionWeeks789 Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: pooled analysis of consecutive cohorts (C-144–01 study)
Sarnaik A, Lewis K, Kluger H, Hamid O, Whitman E, Thomas S, Wermke M, Cusnir M, Domingo-Musibay E, Phan G, Kirkwood J, Hassel J, Orloff M, Larkin J, Weber J, Furness A, Khushalani N, Medina T, Finckenstein F, Jagasia M, Hari P, Sulur G, Shi W, Wu X, Chesney J. 789 Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: pooled analysis of consecutive cohorts (C-144–01 study). 2022, a821-a822. DOI: 10.1136/jitc-2022-sitc2022.0789.Peer-Reviewed Original Research844P Efficacy and safety of lifileucel, an investigational autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma previously treated with anti-LAG3 antibody
Larkin J, Dalle S, Sanmamed M, Wilson M, Hassel J, Kluger H, Orloff M, Weber J, Finckenstein F, Hari P, Jagasia M, Yin H, Shi W, Sulur G, Wu X, Gontcharova V, Lewis K. 844P Efficacy and safety of lifileucel, an investigational autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma previously treated with anti-LAG3 antibody. Annals Of Oncology 2022, 33: s935-s936. DOI: 10.1016/j.annonc.2022.07.970.Peer-Reviewed Original Research
2021
Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma
Zhu G, Su H, Johnson CH, Khan SA, Kluger H, Lu L. Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma. European Journal Of Cancer 2021, 151: 25-34. PMID: 33962358, PMCID: PMC8184628, DOI: 10.1016/j.ejca.2021.03.053.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBacteriaBacterial LoadBacterial TranslocationChemokinesClostridialesCytotoxicity, ImmunologicFemaleGastrointestinal MicrobiomeHumansLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedPrognosisSkin NeoplasmsT-Lymphocytes, CytotoxicTumor MicroenvironmentYoung AdultConceptsT cellsCutaneous melanomaPatient survivalGut microbiomeAdjusted hazard ratioT cell infiltrationChemokine gene expressionChemokine levelsCytotoxic CD8Hazard ratioSystemic inflammationShorter survivalCCL5 expressionPatient outcomesCD8Immune responseMortality riskGut microbiotaSurvival analysisMelanomaTumor nicheHuman cancersSurvivalSignificant correlationPositive association