2024
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances tumor rejection by anti-CTLA-4 immunotherapy in renal cell carcinoma
D.A. Schoenfeld, D. Djureinovic, D.G. Su, L. Zhang, B.Y. Lu, L. Kamga, J.E. Mann, J. Huck, M. Hurwitz, D.A.Braun, L. Jilaveanu, A. Ring, H.M. Kluger. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances tumor rejection by anti-CTLA-4 immunotherapy in renal cell carcinoma. (The Journal of Clinical Investigation, Under review)Peer-Reviewed Original Research In PressHLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases.
Vilariño N, Lopez De Rodas M, Ranjan K, Costantini A, Villalba M, Lu B, Kravitz C, Nadal E, Goldberg S, Nguyen D, Schalper K. HLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases. Journal Of Clinical Oncology 2024, 42: e14014-e14014. DOI: 10.1200/jco.2024.42.16_suppl.e14014.Peer-Reviewed Original ResearchLung cancer brain metastasisPrimary lung tumorsTumor-infiltrating lymphocytesImmune checkpoint inhibitorsCancer brain metastasesAntigen presentation machineryB2M expressionIFN-gBrain metastasesB2MImmune evasionAssociated with shorter overall survivalMultiplexed quantitative immunofluorescenceM expressionExpression of B2MB2M levelsExpression of pSTAT1Shorter overall survivalUnfavorable clinical featuresNo significant associationAssociated with unfavorable clinical featuresCheckpoint inhibitorsImmunotherapy resistanceProperties of tumorsPresentation machineryGut-derived IFNγ-secreting CD4 T cells migrate to the brain and regulate adaptive behavior in a food-deprived state
3. T.M. Yoshida, M. Nguyen, L. Zhang, B.Y. Lu, B. Zhu, K. Murray, Y.S. Mineur, C. Zhang, E. Lin, D.A. Waizman, M. Coden, Y. Ma, K. Israni-Winger, A. Russo, H. Wang, W. Song, J. Al Souz, H. Zhao, J.E. Craft, M.R. Picciotto, J. Grutzendler, N. W. Palm, D.A. Hafler, A. Wang. (Nature, in revisions)Peer-Reviewed Original Research In PressCirculating Tumor Reactive KIR+CD8+ T cells Suppress Anti-Tumor Immunity in Patients with Melanoma
Lu BY, Lucca LE, Lewis W, Wang J, Nogeuira C, Heer S, Axisa PA, Buitrago-Pocasangre N, Pham GP, Kojima ML, Wei W, Aizenbud L, Bacchiocchi A, Zhang L, Walewski J, Chiang VC, Olino K, Clune J, Halaban R, Kluger Y, Coyle AJ, Kisielow J, Obermair FJ, Kluger HM, Hafler DA. Research Square. 2024. DOI: https://doi.org/10.21203/rs.3.rs-3956671/v1.Peer-Reviewed Original Research In Press
2023
Chemoimmunotherapy for Untreated Lung Cancer Brain Metastases: Systemic Before Local Therapy?
Lu BY, Goldberg SB. Chemoimmunotherapy for Untreated Lung Cancer Brain Metastases: Systemic Before Local Therapy? J Clin Oncol 2023, JCO2301323. PMID: 37603819, DOI: 10.1200/JCO.23.01323.Commentaries, Editorials and LettersBSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES
Vilarino N, de Rodas M, Lu B, Goldberg S, Schalper K. BSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402438, DOI: 10.1093/noajnl/vdad070.012.Peer-Reviewed Original ResearchLung cancer brain metastasesPrimary lung tumorsImmune checkpoint inhibitorsCancer brain metastasesBrain metastasesPresentation machineryClinicopathologic variablesHLA classTumor cell PD-L1 expressionBackground Immune checkpoint inhibitorsLocal adaptive immune responseHLA Class I AntigenPD-L1 expressionDuration of responseB2MAdaptive immune responsesDistinct immunomodulatory propertiesImmune evasion mechanismsClass I AntigenIFN-γ signalingIRF-1Interferon regulatory factor 1Checkpoint inhibitorsMost patientsWorse survivalBSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structuresBeyond the Lab and Into the Hospital: An Outlook on the Clinical Utility of Spatial Omics Technologies
Pucciarelli DM, Lu BY, Zlobec I, DiStasio M. Beyond the Lab and Into the Hospital: An Outlook on the Clinical Utility of Spatial Omics Technologies. GEN Biotechnology. Oct 2023.360-371. http://doi.org/10.1089/genbio.2023.0030Commentaries, Editorials and Letters
2022
TCR-sequencing in cancer and autoimmunity: barcodes and beyond
Pauken KE, Lagattuta KA, Lu BY, Lucca LE, Daud AI, Hafler DA, Kluger HM, Raychaudhuri S, Sharpe AH. TCR-sequencing in cancer and autoimmunity: barcodes and beyond. Trends In Immunology 2022, 43: 180-194. PMID: 35090787, PMCID: PMC8882139, DOI: 10.1016/j.it.2022.01.002.Peer-Reviewed Original ResearchConceptsT cell receptorT cellsMolecular barcodesProgrammed Death-1 BlockadeTCR sequencesDeath-1 blockadeUnique TCR sequencesNaïve T cellsT cell functionCell divisionMolecular phenotypesBarcodesImmune responseAntigen specificitySingle cellsCell receptorCell functionRecent technological advancesCancerTCR dataCellsNeurological complications of lung cancer
Kaulen LD, Lu BY, Goldberg SB, Baehring JM, Chapter 15 - Neurological complications of lung cancer, Editor(s): Herbert B. Newton, Mark G. Malkin, Neurological Complications of Systemic Cancer and Antineoplastic Therapy (Second Edition), Academic Press, 2022, Pages 243-276, DOI: 10.1016/b978-0-12-821976-8.00027-xChapters
2021
Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases
Lu BY, Gupta R, Aguirre-Ducler A, Gianino N, Wyatt H, Ribeiro M, Chiang VL, Contessa JN, Adeniran AJ, Jilaveanu LB, Kluger HM, Schalper KA, Goldberg SB. Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases. Journal For ImmunoTherapy Of Cancer 2021, 9: e002684. PMID: 34670827, PMCID: PMC8529973, DOI: 10.1136/jitc-2021-002684.Peer-Reviewed Original ResearchConceptsPrimary lung tumorsT cell subsetsMajor T cell subsetsMultiplexed quantitative immunofluorescenceLung tumorsT cellsCoinhibitory receptorsTim-3Cell subsetsBrain metastasesQuantitative immunofluorescenceHigh LAG-3 expressionTumor PD-L1 expressionPD-L1 protein expressionLymphocyte activation gene-3Low T cell infiltrationHigh TIM-3Major clinicopathological variablesPD-L1 expressionLAG-3 expressionT cell infiltrationTumor-infiltrating lymphocytesLonger overall survivalCell death 1Tumor immune microenvironmentIntracranial Complications From Immune Checkpoint Therapy in a Patient With NSCLC and Multiple Sclerosis: Case Report
Lu BY, Isitan C, Mahajan A, Chiang V, Huttner A, Mitzner JR, Wesley SF, Goldberg SB. Intracranial Complications From Immune Checkpoint Therapy in a Patient With NSCLC and Multiple Sclerosis: Case Report. JTO Clinical And Research Reports 2021, 2: 100183. PMID: 34590030, PMCID: PMC8474265, DOI: 10.1016/j.jtocrr.2021.100183.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsMultiple sclerosisRadiation necrosisBrain lesionsWhole-brain radiation therapyImmune checkpoint therapyViable tumor cellsPaucity of dataBrain metastasesCheckpoint inhibitorsMetastatic NSCLCAdverse eventsCheckpoint therapyDurable responsesNeurologic declineRadiographic benefitIntracranial complicationsPathologic findingsAutoimmune disordersAutoimmune diseasesCase reportIntracranial diseaseRadiation therapyStereotactic radiosurgeryAnticancer benefitsClinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells
Tran TT, Rane CK, Zito CR, Weiss SA, Jessel S, Lucca L, Lu BY, Oria VO, Adeniran A, Chiang VL, Omay SB, Hafler DA, Kluger HM, Jilaveanu LB. Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells. Cancers 2021, 13: 1049. PMID: 33801444, PMCID: PMC7958624, DOI: 10.3390/cancers13051049.Peer-Reviewed Original ResearchPDCD4 expressionImproved survivalTumor-Associated Immune CellsTumor microenvironmentNeoplastic progressionBrain metastasis outcomesExtracranial metastatic diseaseMelanoma brain metastasesNatural killer cellsBrain metastasis samplesImmune cell infiltrationImmune cell subsetsMultiple tissue microarraysExpression of PDCD4Brain metastasesMetastatic diseaseClinical outcomesKiller cellsClinicopathological variablesIntracranial metastasesCell subsetsCell infiltrationCell death 4Immune cellsPrimary melanomaCirculating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
2020
PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice
Eguren-Santamaria I, Sanmamed MF, Goldberg SB, Kluger HM, Idoate MA, Lu B, Corral J, Schalper KA, Herbst RS, Gil-Bazo I. PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice. Clinical Cancer Research 2020, 26: 4186-4197. PMID: 32354698, DOI: 10.1158/1078-0432.ccr-20-0798.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsAnti-PD-1/PD-L1 antibodiesAdvanced non-small cell lung cancerNSCLC brain metastasesBrain metastasesPD-L1 antibodiesAnti-PD-1/PD-L1 agentsPD-1/PD-L1 blockersActive central nervous system (CNS) involvementHigh PD-L1 expressionAnti-PD-1/PD-L1 drugsCentral nervous system involvementPivotal phase III trialsActive brain metastasesCNS response ratesPD-L1 agentsPD-L1 blockersSystemic therapy combinationsNervous system involvementPD-L1 expressionPhase III trialsSubset of patientsCell lung cancerPD-L1 drugs
2019
Functional profile and clinical significance of major tumor infiltrating lymphocyte subsets in lung cancer-associated brain metastases.
Lu B, Gupta R, Stewart T, Kluger H, Jilaveanu L, Schalper K, Goldberg S. Functional profile and clinical significance of major tumor infiltrating lymphocyte subsets in lung cancer-associated brain metastases. Journal Of Clinical Oncology 2019, 37: 2066-2066. DOI: 10.1200/jco.2019.37.15_suppl.2066.Peer-Reviewed Original ResearchPrimary lung tumorsMajor T cell subsetsMultiplexed quantitative immunofluorescenceT cell subsetsExtracranial metastasesT cellsLung tumorsBrain metastasesQuantitative immunofluorescenceAdaptive anti-tumor responsesLow T cell infiltrationMajor clinicopathologic variablesYale Cancer CenterAdaptive immune cellsRegulatory T cellsT cell infiltrationAnti-tumor responseLonger overall survivalOptimal treatment strategyLung cancer patientsKi-67 levelsLung cancer histologyLymphocyte subsetsOverall survivalPrimary malignancy
2018
Heterogeneity within the PF-EPN-B ependymoma subgroup
Cavalli FMG, Hübner JM, Sharma T, Luu B, Sill M, Zapotocky M, Mack SC, Witt H, Lin T, Shih DJH, Ho B, Santi M, Emery L, Hukin J, Dunham C, McLendon RE, Lipp ES, Gururangan S, Grossbach A, French P, Kros JM, van Veelen MC, Rao AAN, Giannini C, Leary S, Jung S, Faria CC, Mora J, Schüller U, Alonso MM, Chan JA, Klekner A, Chambless LB, Hwang EI, Massimino M, Eberhart CG, Karajannis MA, Lu B, Liau LM, Zollo M, Ferrucci V, Carlotti C, Tirapelli DPC, Tabori U, Bouffet E, Ryzhova M, Ellison DW, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Pfister SM, Taylor MD, Aldape K, Pajtler KW, Kool M, Ramaswamy V. Heterogeneity within the PF-EPN-B ependymoma subgroup. Acta Neuropathologica 2018, 136: 227-237. PMID: 30019219, PMCID: PMC6373486, DOI: 10.1007/s00401-018-1888-x.Peer-Reviewed Original ResearchConceptsGenome-wide methylation dataPFA ependymomasChromosome 13q lossDNA methylation profilingGene expression profilesGene expression profilingCopy number profilingBroad copy-number aberrationsCopy number alterationsCopy number aberrationsMethylation profilingExpression profilingExpression profilesDistinct molecular variantsMethylation dataIntegrated analysisDistinct molecular subtypesMolecular variantsProfilingT-SNE analysisMolecular heterogeneityRobust markerPF-EPNNovel markerBiological heterogeneityPD-L1 expression and tumor-infiltrating lymphocytes in lung cancer brain metastases.
Lu B, Gupta R, Ribeiro M, Stewart T, Chiang V, Contessa J, Adeniran A, Kluger H, Jilaveanu L, Schalper K, Goldberg S. PD-L1 expression and tumor-infiltrating lymphocytes in lung cancer brain metastases. Journal Of Clinical Oncology 2018, 36: e24116-e24116. DOI: 10.1200/jco.2018.36.15_suppl.e24116.Peer-Reviewed Original Research
2016
Decitabine enhances chemosensitivity of early T-cell precursor-acute lymphoblastic leukemia cell lines and patient-derived samples.
Lu BY, Thanawala SU, Zochowski KC, Burke MJ, Carroll WL, Bhatla T. Decitabine enhances chemosensitivity of early T-cell precursor-acute lymphoblastic leukemia cell lines and patient-derived samples. Leukemia & Lymphoma 2016, 57: 1938-41. PMID: 26726842, DOI: 10.3109/10428194.2015.1110747.Peer-Reviewed Original Research