Featured Publications
Human Immunodeficiency Virus Is Associated With Poor Overall Survival Among Patients With Head and Neck Cancer
Salahuddin S, Cohen O, Wu M, Irizarry J, Vega T, Gan G, Deng Y, Isaeva N, Prasad M, Schalper K, Mehra S, Yarbrough W, Emu B. Human Immunodeficiency Virus Is Associated With Poor Overall Survival Among Patients With Head and Neck Cancer. Clinical Infectious Diseases 2022, 76: 1449-1458. PMID: 36520995, PMCID: PMC10319962, DOI: 10.1093/cid/ciac924.Peer-Reviewed Original ResearchConceptsOverall survivalIndependent predictorsHNSCC patientsWorse prognosisOropharyngeal tumorsCox proportional hazards regression modelMultivariate analysisHPV-positive oropharyngeal tumorsNeck squamous cell cancerProportional hazards regression modelsLower median overall survivalAcademic hospital centerNon-HIV populationMedian overall survivalPredictors of survivalSquamous cell cancerHuman immunodeficiency virusPoor clinical outcomeExpression of CD4Poor overall survivalHazards regression modelsRace/ethnicityCD8 infiltrationHazard ratioClinicopathologic characteristicsPatients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis
Chaudhary O, Trotta D, Wang K, Wang X, Chu X, Bradley C, Okulicz J, Maves RC, Kronmann K, Schofield CM, Blaylock JM, Deng Y, Schalper KA, Kaech SM, Agan B, Ganesan A, Emu B. Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis. Journal For ImmunoTherapy Of Cancer 2022, 10: e004564. PMID: 35470232, PMCID: PMC9039380, DOI: 10.1136/jitc-2022-004564.Peer-Reviewed Original ResearchConceptsViral suppressionTraditional risk factorsCase-control study designMarker of riskControl study designHIV infectionStudy cohortInhibitory receptorsRisk factorsCancer casesT cellsStudy designCancer diagnosisPLWHHIVCancerRiskCD4CellsPatientsTranscription factorsClinical cancer diagnosisCohortSuppressionInfectionCancer Microbiology
DiMaio D, Emu B, Goodman AL, Mothes W, Justice A. Cancer Microbiology. Journal Of The National Cancer Institute 2021, 114: 651-663. PMID: 34850062, PMCID: PMC9086797, DOI: 10.1093/jnci/djab212.Peer-Reviewed Original ResearchConceptsDirect carcinogenic effectSpecific immune interactionsMiddle-income countriesCancer controlCancer preventionInfection controlImmune interactionsCancerCancer treatmentCarcinogenic effectsExposure reductionDrug developmentCancer formationPublic healthTreatmentHuman microbiomeCross-disciplinary trainingVaccineAntiviralsPreventionImportant roleUptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors
Xu S, Chaudhary O, Rodríguez-Morales P, Sun X, Chen D, Zappasodi R, Xu Z, Pinto AFM, Williams A, Schulze I, Farsakoglu Y, Varanasi SK, Low JS, Tang W, Wang H, McDonald B, Tripple V, Downes M, Evans RM, Abumrad NA, Merghoub T, Wolchok JD, Shokhirev MN, Ho PC, Witztum JL, Emu B, Cui G, Kaech SM. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors. Immunity 2021, 54: 1561-1577.e7. PMID: 34102100, PMCID: PMC9273026, DOI: 10.1016/j.immuni.2021.05.003.Peer-Reviewed Original ResearchConceptsTumor microenvironmentCell dysfunctionLipid peroxidationLipid accumulationOxidized low-density lipoproteinExpression of CD36Low-density lipoproteinCommon metabolic alterationsScavenger receptor CD36Intratumoral CD8Immune dysfunctionEffector TGlutathione peroxidase 4CD8Effector functionsInhibition of p38Metabolic alterationsReceptor CD36Therapeutic avenuesScavenger receptorsDysfunctionWT counterpartsTILsCell functionCD36Decreased Overall Survival in HIV-associated Non–small-cell Lung Cancer
Hysell K, Yusuf R, Barakat L, Virata M, Gan G, Deng Y, Perez-Irizarry J, Vega T, Goldberg SB, Emu B. Decreased Overall Survival in HIV-associated Non–small-cell Lung Cancer. Clinical Lung Cancer 2020, 22: e498-e505. PMID: 33468393, PMCID: PMC8169710, DOI: 10.1016/j.cllc.2020.11.006.Peer-Reviewed Original ResearchConceptsCell lung cancerGeneral patientsNSCLC populationLung cancerCox proportional hazards modelYale-New Haven HospitalGeneral NSCLC populationOutcomes of patientsOverall median survivalRetrospective cohort studyPredictors of survivalKaplan-Meier curvesHIV-1 RNACopies/mLLog-rank testProportional hazards modelNew Haven HospitalCancer treatment regimensMedian CD4Antiretroviral therapyCohort studyMedian survivalOverall survivalHIV infectionMedian age661. Ibalizumab Efficacy and Safety Through 48 Weeks of Treatment: Results of an Expanded Access Protocol (TMB-311)
Emu B, DeJesus E, Berhe M, Leider J, Creticos C, Weinheimer S, Cohen Z. 661. Ibalizumab Efficacy and Safety Through 48 Weeks of Treatment: Results of an Expanded Access Protocol (TMB-311). Open Forum Infectious Diseases 2019, 6: s303-s303. PMCID: PMC6811265, DOI: 10.1093/ofid/ofz360.729.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsWeeks of treatmentCopies/mLViral loadCopies/Cohort 2Multidrug-resistant HIV-1 infectionDay 0HIV-1 RNA levelsImmune reconstitution inflammatory syndromeLog10 copies/mLHIV-1 viral loadPivotal phase 3 studiesCohort 2 patientsDurable viral suppressionMajor eligibility criteriaReconstitution inflammatory syndromeWeek 24 visitCD4 cell countMedian viral loadTreatment-experienced patientsCells/mm3Phase 3 studyInjection site reactionsLog10 copies/437 Safety and efficacy of immune checkpoint inhibitors (ICI) in patients living with HIV (PLWH) and metastatic non-small cell lung cancer (NSCLC): a matched cohort study from the international CATCH-IT consortium
Zarif T, Nassar A, Adib E, Fitzgerald B, Huang J, Mouhieddine T, Nonato T, McKay R, Li M, Mittra A, Owen D, Lorentsen M, Dittus C, Dizman N, Emu B, Falohun A, Abdel-Wahab N, Bankapur A, Reed A, Dobbs R, Kim C, Arora A, Shah N, El-Am E, Kozaily E, Abdallah W, Al-Hader A, Ghazal B, Saeed A, Drolen C, Lechner M, Espinar J, Nebhan C, Johnson D, Haykal T, Morse M, Cortellini A, Pinato D, Pria A, Bower M, Hall E, Bakalov V, Bahary N, Rajkumar A, Mangla A, Shah V, Singh P, Nana F, Lia N, Dima D, Funchain P, Saleem R, Woodford R, Long AO G, Menzies A, Genova C, Barletta G, Puri S, Florou V, Idossa D, Queirolo P, Lamberti G, Addeo A, Bersanelli M, Freeman D, Xie W, Ramaswami R, Marron T, Choueiri T, Lurain K, Baden L, Sonpavde G, Naqash A. 437 Safety and efficacy of immune checkpoint inhibitors (ICI) in patients living with HIV (PLWH) and metastatic non-small cell lung cancer (NSCLC): a matched cohort study from the international CATCH-IT consortium. 2022, a457-a458. DOI: 10.1136/jitc-2022-sitc2022.0437.Peer-Reviewed Original ResearchThe β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell functionInfection with alternate frequencies of SARS-CoV-2 vaccine boosting for patients undergoing antineoplastic cancer treatments
Townsend J, Hassler H, Emu B, Dornburg A. Infection with alternate frequencies of SARS-CoV-2 vaccine boosting for patients undergoing antineoplastic cancer treatments. Journal Of The National Cancer Institute 2023, 115: 1626-1628. PMID: 37599438, PMCID: PMC10699797, DOI: 10.1093/jnci/djad158.Peer-Reviewed Original ResearchConceptsReinfection riskAntineoplastic therapyAntibody dataSARS-CoV-2 infectionSARS-CoV-2 vaccinesChemotherapy-immunotherapy combinationsPfizer-BioNTech BNT162b2COVID-19 vaccinationHigh infection riskFrequent boostingRituximab therapyBreakthrough infectionsVaccination scheduleAntibody levelsBooster scheduleVaccination frequencyImmune responseAdditional interventionsReduced riskHigh riskHormonal treatmentGeneral populationNecessitating assessmentPatientsInfection risk
2023
1014 Adrenergic receptors regulate T cell differentiation in viral infection and cancer
Globig A, Zhao S, Roginsky J, Avina-Ochoa N, Heeg M, Chaudhary O, Hoffmann F, Chen D, O’Connor C, Emu B, Kaech S. 1014 Adrenergic receptors regulate T cell differentiation in viral infection and cancer. 2023, a1122-a1122. DOI: 10.1136/jitc-2023-sitc2023.1014.Peer-Reviewed Original ResearchImpact of Head and Neck Cancer Treatment on CD4 T Cell Decline and Recovery in People with HIV
Hicks D, Salahuddin S, Wu M, Perez-Irizarry J, Emu B, Park H. Impact of Head and Neck Cancer Treatment on CD4 T Cell Decline and Recovery in People with HIV. International Journal Of Radiation Oncology • Biology • Physics 2023, 117: e588. DOI: 10.1016/j.ijrobp.2023.06.1934.Peer-Reviewed Original ResearchCells/mm3CD4 countPercentage of baselineMann-Whitney testCD4 T-cell declineMedian baseline CD4 countMedian nadir CD4 countCancer treatmentBaseline CD4 countCancer treatment initiationMedian baseline CD4Treatment-related immunosuppressionNadir CD4 countMajority of patientsRetrospective chart reviewTime of diagnosisStart of treatmentT-cell declineNeck cancer treatmentMATERIAL/METHODSNonparametric Mann-Whitney testBaseline CD4Immunologic declineMedian CD4Antiretroviral therapySafety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium
El Zarif T, Nassar A, Adib E, Fitzgerald B, Huang J, Mouhieddine T, Rubinstein P, Nonato T, McKay R, Li M, Mittra A, Owen D, Baiocchi R, Lorentsen M, Dittus C, Dizman N, Falohun A, Abdel-Wahab N, Diab A, Bankapur A, Reed A, Kim C, Arora A, Shah N, El-Am E, Kozaily E, Abdallah W, Al-Hader A, Abu Ghazal B, Saeed A, Drolen C, Lechner M, Drakaki A, Baena J, Nebhan C, Haykal T, Morse M, Cortellini A, Pinato D, Dalla Pria A, Hall E, Bakalov V, Bahary N, Rajkumar A, Mangla A, Shah V, Singh P, Aboubakar Nana F, Lopetegui-Lia N, Dima D, Dobbs R, Funchain P, Saleem R, Woodford R, Long G, Menzies A, Genova C, Barletta G, Puri S, Florou V, Idossa D, Saponara M, Queirolo P, Lamberti G, Addeo A, Bersanelli M, Freeman D, Xie W, Reid E, Chiao E, Sharon E, Johnson D, Ramaswami R, Bower M, Emu B, Marron T, Choueiri T, Baden L, Lurain K, Sonpavde G, Naqash A. Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium. Journal Of Clinical Oncology 2023, 41: 3712-3723. PMID: 37192435, PMCID: PMC10351941, DOI: 10.1200/jco.22.02459.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsProgression-free survivalObjective response rateOverall survivalMetastatic NSCLCCheckpoint inhibitorsGrade immune-related adverse eventsImmune checkpoint inhibitor trialsNeck squamous cell carcinomaActivity of ICICheckpoint inhibitor trialsCohort of PWHImmune checkpoint inhibitorsHIV viral loadKaplan-Meier methodSquamous cell carcinomaUse of ICIMean survival timeMost common cancersL1 monotherapyRECIST 1.1Adverse eventsInhibitor trialsMedian ageAdvanced cancerAdrenergic receptors regulate T cell differentiation in viral infection and cancer
Globig A, Zhao S, Roginsky J, Avina-Ochoa N, Heeg M, Chaudhary O, Hoffmann F, Chen D, O’Connor C, Emu B, Kaech S. Adrenergic receptors regulate T cell differentiation in viral infection and cancer. The Journal Of Immunology 2023, 210: 59.13-59.13. DOI: 10.4049/jimmunol.210.supp.59.13.Peer-Reviewed Original ResearchImmune checkpoint blockadeT cell differentiationChronic viral infectionsT cell functionalityT cellsViral infectionAdrenergic receptorsChronic antigen exposureLCMV clone 13Novel immune checkpointT cell proliferationMurine cancer modelsT cell receptor signalingCell differentiationAbstract CD8Terminal-CD8Exhausted CD8Checkpoint blockadeAntigen exposureImmune checkpointsNoradrenaline levelsCell receptor signalingTumor sizeCancer patientsNA receptorsBuilding an Infectious Disease Diversity, Equity, and Antiracism (ID2EA) Curriculum: A Single Center's Experience and Reflections
Gleeson S, Zapata H, Bathgate M, Emu B, Frederick J, Friedland G, Golden M, Meyer J, Radin J, Sideleau R, Shaw A, Shenoi S, Trubin P, Virata M, Barakat L, Desruisseaux M. Building an Infectious Disease Diversity, Equity, and Antiracism (ID2EA) Curriculum: A Single Center's Experience and Reflections. Clinical Infectious Diseases 2023, 77: 703-710. PMID: 37078888, DOI: 10.1093/cid/ciad236.Peer-Reviewed Original ResearchConceptsEducational activitiesHealthcare inequitiesInfectious Diseases SectionSingle-center experienceCoronavirus disease 2019 (COVID-19) pandemicDisease 2019 pandemicMixed-methods assessmentLearning objectivesPilot curriculumEducational trainingCurriculumCenter experienceLong-term behavioral changesProgram outcomesDisease sectionDisease diversityPhysician perspectivesResponse rateHealth disparitiesYale SchoolInequitiesAntiracismBehavioral changesRacismEquityPD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2022
Impact of HIV infection on clinical outcomes among people diagnosed with head and neck cancer.
Salahuddin S, Cohen O, Wu M, Irizarry J, Vega T, Gan G, Deng Y, Isaeva N, Schalper K, Mehra S, Yarbrough W, Emu B. Impact of HIV infection on clinical outcomes among people diagnosed with head and neck cancer. Journal Of Clinical Oncology 2022, 40: e18080-e18080. DOI: 10.1200/jco.2022.40.16_suppl.e18080.Peer-Reviewed Original ResearchOropharyngeal squamous cell carcinomaCD8 T cell infiltrationPD-L1 expressionUninfected patientsT cell infiltrationPoor outcomeHNC patientsInsurance statusRace/ethnicityMedian survivalQuantitative immunofluorescenceIndependent predictorsClinical outcomesViral loadCell infiltrationNeck cancerAnatomic sitesTobacco useMultivariate analysisLow PD-L1 expressionCombination antiretroviral therapy eraTumor microenvironmentAntiretroviral therapy eraMedian CD4 countHIV viral load
2021
Palliation of malignancies in HIV infection
Yasin F, Chow R, Emu B, Bui T, Prsic E. Palliation of malignancies in HIV infection. BMJ Supportive & Palliative Care 2021, bmjspcare-2021-003179. PMID: 34006512, DOI: 10.1136/bmjspcare-2021-003179.Peer-Reviewed Original ResearchNASH limits anti-tumour surveillance in immunotherapy-treated HCC
Pfister D, Núñez NG, Pinyol R, Govaere O, Pinter M, Szydlowska M, Gupta R, Qiu M, Deczkowska A, Weiner A, Müller F, Sinha A, Friebel E, Engleitner T, Lenggenhager D, Moncsek A, Heide D, Stirm K, Kosla J, Kotsiliti E, Leone V, Dudek M, Yousuf S, Inverso D, Singh I, Teijeiro A, Castet F, Montironi C, Haber PK, Tiniakos D, Bedossa P, Cockell S, Younes R, Vacca M, Marra F, Schattenberg JM, Allison M, Bugianesi E, Ratziu V, Pressiani T, D’Alessio A, Personeni N, Rimassa L, Daly AK, Scheiner B, Pomej K, Kirstein MM, Vogel A, Peck-Radosavljevic M, Hucke F, Finkelmeier F, Waidmann O, Trojan J, Schulze K, Wege H, Koch S, Weinmann A, Bueter M, Rössler F, Siebenhüner A, De Dosso S, Mallm JP, Umansky V, Jugold M, Luedde T, Schietinger A, Schirmacher P, Emu B, Augustin HG, Billeter A, Müller-Stich B, Kikuchi H, Duda DG, Kütting F, Waldschmidt DT, Ebert MP, Rahbari N, Mei HE, Schulz AR, Ringelhan M, Malek N, Spahn S, Bitzer M, Ruiz de Galarreta M, Lujambio A, Dufour JF, Marron TU, Kaseb A, Kudo M, Huang YH, Djouder N, Wolter K, Zender L, Marche PN, Decaens T, Pinato DJ, Rad R, Mertens JC, Weber A, Unger K, Meissner F, Roth S, Jilkova ZM, Claassen M, Anstee QM, Amit I, Knolle P, Becher B, Llovet JM, Heikenwalder M. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 2021, 592: 450-456. PMID: 33762733, PMCID: PMC8046670, DOI: 10.1038/s41586-021-03362-0.Peer-Reviewed Original ResearchConceptsNon-alcoholic steatohepatitisNon-viral hepatocellular carcinomaAnti-PD1 treatmentT cellsHepatocellular carcinomaNASH-HCCImmune surveillanceRandomized phase III clinical trialsPhase III clinical trialsAberrant T cell activationAnti-PDL1 treatmentAnti-tumor surveillanceStudy of immunotherapyDepletion of CD8Advanced hepatocellular carcinomaTumor immune surveillanceStratification of patientsBiomarker-based stratificationT cell activationAdjuvant treatmentOverall survivalTNF neutralizationDeath-1Immune therapyTherapeutic immunotherapy
2019
Exosomal MicroRNAs Associate With Neuropsychological Performance in Individuals With HIV Infection on Antiretroviral Therapy.
OʼMeara T, Kong Y, Chiarella J, Price RW, Chaudhury R, Liu X, Spudich S, Robertson K, Emu B, Lu L. Exosomal MicroRNAs Associate With Neuropsychological Performance in Individuals With HIV Infection on Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2019, 82: 514-522. PMID: 31714431, PMCID: PMC6857839, DOI: 10.1097/qai.0000000000002187.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyNeuropsychological performanceAntiretroviral therapyViral suppressionHIV infectionNeurocognitive dysfunctionExo-miRNAsEarly infection groupCentral nervous systemSystemic viral suppressionTyrosine receptor kinaseInfection groupChronic infectionPLWHCross-sectional examinationNervous systemEarly infectionNeuropsychological scoresInfectionConsistent findingNeuropsychological batteryHIVNeurodegeneration pathwaysDysfunctionTherapyP1.04-23 Characterizing the Tumor Immune Microenvironment of Non-Small Cell Lung Carcinoma in People Living with HIV Using Imaging Mass Cytometry
Yusuf R, Villarroel-Espindola F, Schalper K, Emu B. P1.04-23 Characterizing the Tumor Immune Microenvironment of Non-Small Cell Lung Carcinoma in People Living with HIV Using Imaging Mass Cytometry. Journal Of Thoracic Oncology 2019, 14: s448. DOI: 10.1016/j.jtho.2019.08.926.Peer-Reviewed Original Research