2024
Genomic and Immunophenotypic Characteristics of Conjunctival Squamous Cell Carcinoma in a Sub-Saharan African Cohort Suggest a Role for Immune Checkpoint Inhibitors in Locally Advanced or Metastatic Patients
Esmaeli B, Gleber-Netto F, Sagiv O, Pickering C, Gross N, Ning J, Yeshi M, Mitku Y, Nagarajan P. Genomic and Immunophenotypic Characteristics of Conjunctival Squamous Cell Carcinoma in a Sub-Saharan African Cohort Suggest a Role for Immune Checkpoint Inhibitors in Locally Advanced or Metastatic Patients. JCO Global Oncology 2024, 10: 85-86. DOI: 10.1200/go-24-72000.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsTumor mutational burdenConjunctival squamous cell carcinomaHigh-risk human papillomavirusSquamous cell carcinomaCheckpoint inhibitorsMetastatic patientsCell carcinomaImmunophenotypic characteristicsHigh risk human papillomavirus statusImmune checkpoint inhibitor therapyDensity of CD8+Sub-Saharan African cohortsPD-L1 expressionTumor-infiltrating lymphocytesCD3+ cellsTumors of patientsSub-Saharan AfricaWhole-exome sequencingSCC subtypePD-L1Thicker tumorsCD8+Clinical responseMutational burdenImmune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer
Michikawa C, Gleber-Netto F, Pickering C, Rao X, Wang J, Sikora A, Myers J, Frederick M. Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer. Oral Oncology 2024, 153: 106729. PMID: 38663156, DOI: 10.1016/j.oraloncology.2024.106729.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaAssociated with clinical outcomesExtranodal extensionLymph node metastasisImmune infiltrationImmune infiltration statusOverall survivalPrimary tumorNode metastasisOral cancerInfiltration statusClinical outcomes of OSCC patientsExtension of lymph node metastasesAssociated with clinical outcomes of patientsAssociated with OS rateLocally advanced oral cancerClinical outcomes of patientsOutcome of OSCC patientsAssociated with poor overall survivalImmune infiltration of tumorsLow immune infiltrationNode negative tumorsAdvanced oral cancerHuman papillomavirus-negativeInfiltration of tumorsTh2 Cells Are Associated with Tumor Recurrence Following Radiation
Abdelhakiem M, Bao R, Pifer P, Molkentine D, Molkentine J, Hefner A, Beadle B, Heymach J, Luke J, Ferris R, Pickering C, Wang J, Patel R, Skinner H. Th2 Cells Are Associated with Tumor Recurrence Following Radiation. Cancers 2024, 16: 1586. PMID: 38672668, PMCID: PMC11049347, DOI: 10.3390/cancers16081586.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaLocoregional recurrenceValidation cohortTh2 infiltrationDiscovery cohortTh2 cellsTreatment of multiple solid tumorsAssociated with locoregional recurrenceNeck squamous cell carcinomaAssociated with tumor recurrencePrognostic immune biomarkersAntitumor immune responseTumor immune infiltrationSquamous cell carcinomaMultiple solid tumorsIndependent validation cohortResponse to radiationImmune cell typesMechanism of radiation resistanceAssociated with outcomeAdjuvant radiationTumor recurrenceHNSCC tumorsCell carcinomaImmune infiltrationHistologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden
Gleber-Netto F, Nagarajan P, Sagiv O, Pickering C, Gross N, Ning J, Yeshi M, Mitku Y, Tetzlaff M, Esmaeli B. Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden. Investigative Ophthalmology & Visual Science 2024, 65: 24. PMID: 38597722, PMCID: PMC11008748, DOI: 10.1167/iovs.65.4.24.Peer-Reviewed Original ResearchConceptsHigh-risk human papillomavirusTumor mutational burdenMutational burdenHistological featuresHigh risk human papillomavirus statusConjunctival squamous cell carcinomaHigh tumor mutational burdenDensity of CD8+PD-L1 expressionTumor-infiltrating lymphocytesCD3+ cellsTumors of patientsSquamous cell carcinomaWhole-exome sequencingPotential treatment strategySCC subtypeThicker tumorsPD-L1CD8+Cell carcinomaHuman papillomavirusCutaneous SCCGenomic alterationsCancer Genome AtlasTreatment strategiesMutant p53 gains oncogenic functions through a chromosomal instability-induced cytosolic DNA response
Zhao M, Wang T, Gleber-Netto F, Chen Z, McGrail D, Gomez J, Ju W, Gadhikar M, Ma W, Shen L, Wang Q, Tang X, Pathak S, Raso M, Burks J, Lin S, Wang J, Multani A, Pickering C, Chen J, Myers J, Zhou G. Mutant p53 gains oncogenic functions through a chromosomal instability-induced cytosolic DNA response. Nature Communications 2024, 15: 180. PMID: 38167338, PMCID: PMC10761733, DOI: 10.1038/s41467-023-44239-2.Peer-Reviewed Original Research
2023
Deep learning of cell spatial organizations identifies clinically relevant insights in tissue images
Wang S, Rong R, Zhou Q, Yang D, Zhang X, Zhan X, Bishop J, Chi Z, Wilhelm C, Zhang S, Pickering C, Kris M, Minna J, Xie Y, Xiao G. Deep learning of cell spatial organizations identifies clinically relevant insights in tissue images. Nature Communications 2023, 14: 7872. PMID: 38081823, PMCID: PMC10713592, DOI: 10.1038/s41467-023-43172-8.Peer-Reviewed Original ResearchFAK drives resistance to therapy in HPV-negative head and neck cancer in a p53-dependent manner.
Pifer P, Yang L, Kumar M, Xie T, Frederick M, Hefner A, Beadle B, Molkentine D, Molkentine J, Dhawan A, Abdelhakiem M, Osman A, Leibowitz B, Myers J, Pickering C, Sandulache V, Heymach J, Skinner H. FAK drives resistance to therapy in HPV-negative head and neck cancer in a p53-dependent manner. Clinical Cancer Research 2023, 30: 187-197. PMID: 37819945, PMCID: PMC10767302, DOI: 10.1158/1078-0432.ccr-23-0964.Peer-Reviewed Original ResearchConceptsHPV-negative headHPV-negative HNSCC tumorsWorse disease-free survivalNeck squamous cell carcinomaMutant TP53HPV-negative HNSCC cell linesBackbone of therapyDisease-free survivalPlatinum-based chemotherapySquamous cell carcinomaHPV-negative HNSCCHNSCC cell linesCell linesWild-type TP53Cisplatin-resistant cell linesCell carcinomaHNSCC cohortNeck cancerHNSCC tumorsVivo shRNA screenWorse outcomesA Deep Learning Onion Peeling Approach to Measure Oral Epithelium Layer Number
Zhang X, Gleber-Netto F, Wang S, Jin K, Yang D, Gillenwater A, Myers J, Ferrarotto R, Pickering C, Xiao G. A Deep Learning Onion Peeling Approach to Measure Oral Epithelium Layer Number. Cancers 2023, 15: 3891. PMID: 37568707, PMCID: PMC10416878, DOI: 10.3390/cancers15153891.Peer-Reviewed Original ResearchOral epitheliumNeck squamous cell carcinomaSquamous cell carcinomaPatients' qualityCell carcinomaDysplasia severityEarly diagnosisPathologist's examinationOral cavityComplex cancersClinical relevanceDysplasia diagnosisSurvival analysisEpithelium layerDiagnostic potentialCell layerIntra-observer variationDiagnosisEpitheliumClose correlationPotential additionPrognosisCarcinomaCancerDeep learning‐based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia
Zhang X, Gleber‐Netto F, Wang S, Martins‐Chaves R, Gomez R, Vigneswaran N, Sarkar A, William W, Papadimitrakopoulou V, Williams M, Bell D, Palsgrove D, Bishop J, Heymach J, Gillenwater A, Myers J, Ferrarotto R, Lippman S, Pickering C, Xiao G. Deep learning‐based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia. Cancer Medicine 2023, 12: 7508-7518. PMID: 36721313, PMCID: PMC10067069, DOI: 10.1002/cam4.5478.Peer-Reviewed Original ResearchConceptsLow-risk groupOral leukoplakiaOL patientsProgression riskOral mucosaHigh-risk patientsOral cancer developmentRisk stratification modelCancer progression riskLarge interobserver variabilityEarly diagnosisHigh riskDysplasia gradingAbnormal morphological featuresOral epitheliumOC developmentEarly interventionLow-risk onesPatientsStratification modelCancer developmentCancer progressionInterobserver variabilityLeukoplakiaRiskHRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma
Coleman N, Marcelo K, Hopkins J, Khan N, Du R, Hong L, Park E, Balsara B, Leoni M, Pickering C, Myers J, Heymach J, Albacker L, Hong D, Gillison M, Le X. HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma. JCO Precision Oncology 2023, 7: e2200211. PMID: 36603172, PMCID: PMC9928766, DOI: 10.1200/po.22.00211.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaMD Anderson Cancer CenterSquamous cell carcinomaAnderson Cancer CenterCo-occurring mutationsClinical courseSurvival outcomesCancer CenterCell carcinomaShorter disease-free survivalPoor clinic outcomePrimary definitive treatmentTherapeutic combination strategiesDisease-free survivalPoor clinical outcomePatient demographic informationImproved OSDefinitive treatmentMedian ageOverall survivalFoundation MedicineMale patientsClinical outcomesClinic outcomesTreatment response
2022
Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up
Chahoud J, Zacharias N, Pham R, Qiao W, Guo M, Lu X, Alaniz A, Segarra L, Martinez-Ferrer M, Gleber-Netto F, Pickering C, Rao P, Pettaway C. Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up. Cancers 2022, 14: 6024. PMID: 36551510, PMCID: PMC9775956, DOI: 10.3390/cancers14246024.Peer-Reviewed Original ResearchPenile squamous cell carcinomaCancer-specific survivalSquamous cell carcinomaOverall survivalLymphovascular invasionCell carcinomaMedian cancer-specific survivalHigh-risk human papillomavirusHR-HPV statusMedian overall survivalTumor p16 statusHuman papillomavirus (HPV) statusHigh-risk HPVIndependent prognostic factorSingle-institution analysisClinico-pathologic variablesIHC staining patternSitu hybridization kitHR-HPVHPV statusPatient characteristicsPrognostic factorsSpecific survivalMultivariable analysisPrognostic significanceMildly dysplastic oral lesions with optically-detectable abnormalities share genetic similarities with severely dysplastic lesions
Brenes D, Nipper A, Tan M, Gleber-Netto F, Schwarz R, Pickering C, Williams M, Vigneswaran N, Gillenwater A, Sikora A, Richards-Kortum R. Mildly dysplastic oral lesions with optically-detectable abnormalities share genetic similarities with severely dysplastic lesions. Oral Oncology 2022, 135: 106232. PMID: 36335817, PMCID: PMC9881670, DOI: 10.1016/j.oraloncology.2022.106232.Peer-Reviewed Original ResearchConceptsOral premalignant lesionsMild dysplasiaSevere dysplasiaOral lesionsPremalignant lesionsDysplastic oral lesionsHigh-grade pathologySubset of lesionsLoss of autofluorescenceDysplastic lesionsOptical imaging studiesOral surgeryDysplasiaDetectable abnormalitiesPatient careLesionsImaging studiesEpithelial cell nucleiPatientsGene expressionGene expression profilesMarkersGene expression analysisSimilar gene expressionExpression profilesClinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Rodriguez CP, Kang H, Geiger JL, Burtness B, Chung CH, Pickering CR, Fakhry C, Le QT, Yom SS, Galloway TJ, Golemis E, Li A, Shoop J, Wong S, Mehra R, Skinner H, Saba NF, Flores ER, Myers JN, Ford JM, Karchin R, Ferris RL, Kunos C, Lynn JM, Malik S. Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Journal Of The National Cancer Institute 2022, 114: 1619-1627. PMID: 36053203, PMCID: PMC9745425, DOI: 10.1093/jnci/djac163.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaClinical trialsCell carcinomaTrial designTP53 mutationsNational Clinical Trials NetworkMetastatic disease settingsClinical trial developmentClinical Trials NetworkNovel therapeutic approachesNational Cancer InstituteMetastatic headTP53-mutated tumorsWorse outcomesClinical studiesFrequent genetic eventTherapeutic approachesCancer InstituteTrial developmentBreakout groupsPatientsDisease settingsBiomarker integrationTrials NetworkCombined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers.
Ghosh S, Mazumdar T, Xu W, Powell RT, Stephan C, Shen L, Shah PA, Pickering CR, Myers JN, Wang J, Frederick MJ, Johnson FM. Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers. Clinical Cancer Research 2022, 28: 4479-4493. PMID: 35972731, PMCID: PMC9588713, DOI: 10.1158/1078-0432.ccr-22-1627.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAlphapapillomavirusApoptosisATPases Associated with Diverse Cellular ActivitiesAurora KinasesCell Cycle ProteinsFemaleHumansOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsRetinoblastoma ProteinUterine Cervical NeoplasmsConceptsHPV-positive cancer cellsInhibition-induced apoptosisAurora kinase inhibitorsAurora kinase inhibitionCancer cellsKinase inhibitionAbsence of RbViral oncoprotein E7Kinase inhibitorsMitotic exitAAA-ATPaseProtein degradationRb functionMechanisms of sensitivityPathway componentsTRIP13MAD2L1Extensive apoptosisCancer cell linesSquamous cancer cell linesApoptosisCell linesRetinoblastoma expressionBUB1BProtein expression correlatesMutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma
Shi Y, Xie T, Wang B, Wang R, Cai Y, Yuan B, Gleber-Netto FO, Tian X, Rodriguez-Rosario AE, Osman AA, Wang J, Pickering CR, Ren X, Sikora AG, Myers JN, Rangel R. Mutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma. Communications Biology 2022, 5: 757. PMID: 35902768, PMCID: PMC9334280, DOI: 10.1038/s42003-022-03675-4.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaTumor immune microenvironmentCold tumor immune microenvironmentSquamous cell carcinomaICI therapyOSCC modelCell carcinomaImmune microenvironmentCold tumorsCell death protein 1 (PD-1) inhibitorsCancer cell-intrinsic mechanismsImmune checkpoint inhibitor therapyOral squamous cell carcinomaCheckpoint inhibitor therapyCombination ICI treatmentEffective immunotherapeutic approachesInterferon genes (STING) agonistImmunosuppressive M2 macrophagesProtein 1 inhibitorTobacco-associated cancersICI responsivenessICI treatmentCell-intrinsic mechanismsImmunotherapeutic approachesInhibitor therapyHigh enhancer activity is an epigenetic feature of HPV negative atypical head and neck squamous cell carcinoma
Callahan SC, Kochat V, Liu Z, Raman AT, Divenko M, Schulz J, Terranova CJ, Ghosh AK, Tang M, Johnson FM, Wang J, Skinner HD, Pickering CR, Myers JN, Rai K. High enhancer activity is an epigenetic feature of HPV negative atypical head and neck squamous cell carcinoma. Frontiers In Cell And Developmental Biology 2022, 10: 936168. PMID: 35927986, PMCID: PMC9343809, DOI: 10.3389/fcell.2022.936168.Peer-Reviewed Original ResearchNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaCell linesHNSCC cell linesAtypical headResistance pathwaysHNSCC subtypesFrequent recurrenceMolecular subtypesHeterogeneous diseaseLipid metabolismSubtypesSignificant mortalityCarcinomaMAPK signalingFuture targetsHigh enhancer activityDiseaseAtypicalsBromodomain inhibitorsTCGA tumorsEnhancer activityBasalMesenchymalFusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1)
Michikawa C, Gopalakrishnan V, Harrandah AM, Karpinets TV, Garg RR, Chu RA, Park YP, Chukkapallia SS, Yadlapalli N, Erikson-Carter KC, Gleber-Netto FO, Sayour E, Progulske-Fox A, Chan , Wu X, Zhang J, Jobin C, Wargo JA, Pickering CR, Myers JN, Silver N. Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1). Neoplasia 2022, 31: 100813. PMID: 35834946, PMCID: PMC9287628, DOI: 10.1016/j.neo.2022.100813.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAdjacent normal tissuesWhole-exome sequencingNormal tissuesNeck cancerOral tongue squamous cell carcinoma patientsTongue squamous cell carcinoma patientsSquamous cell carcinoma patientsTumor samplesPD-L1 mRNA expressionPD-L1 protein expressionOral tongue SCCCell carcinoma patientsOral tongue cancerImmune cell infiltrationPD-L1 mRNATumor immune microenvironmentNeck SCC cell linesNeck cancer cell linesSCC cell linesDevelopment of headCell linesCancer cell linesTongue SCCCarcinoma patientsEvolutionary Action Score of TP53 Analysis in Pathologically High-Risk Human Papillomavirus-Negative Head and Neck Cancer From a Phase 2 Clinical Trial: NRG Oncology Radiation Therapy Oncology Group 0234
Michikawa C, Torres-Saavedra P, Silver N, Harari P, Kies M, Rosenthal D, Le Q, Jordan R, Duose D, Mallampati S, Trivedi S, Luthra R, Wistuba I, Osman A, Lichtarge O, Foote R, Parvathaneni U, Hayes D, Pickering C, Myers J. Evolutionary Action Score of TP53 Analysis in Pathologically High-Risk Human Papillomavirus-Negative Head and Neck Cancer From a Phase 2 Clinical Trial: NRG Oncology Radiation Therapy Oncology Group 0234. Advances In Radiation Oncology 2022, 7: 100989. PMID: 36420184, PMCID: PMC9677209, DOI: 10.1016/j.adro.2022.100989.Peer-Reviewed Original ResearchDisease-free survivalCisplatin armDocetaxel armOverall survivalPrognostic markerRadiation therapyHigh-risk pathologic featuresHuman papillomavirus-negative headPhase 2 clinical trialPhase 2 studyBetter overall survivalLow-risk groupReliable prognostic markersEvolutionary action scoreAdvanced HNSCCAdjuvant treatmentResection samplesClinical outcomesDistant metastasisPathologic featuresPoor outcomeNeck cancerClinical trialsTreatment outcomesBetter survivalInduction Chemotherapy with or without Erlotinib in Patients with Head and Neck Squamous Cell Carcinoma Amenable for Surgical Resection
Le X, Gleber-Netto FO, Rubin ML, Qing Y, Du R, Kies M, Blumenschein G, Lu C, Johnson FM, Bell D, Lewis J, Zhang J, Feng L, Wilson K, Marcelo-Lewis K, Wang J, Ginsberg L, Gillison M, Lee JJ, Meric-Berstam F, Mills GB, William W, Myers JN, Pickering CR. Induction Chemotherapy with or without Erlotinib in Patients with Head and Neck Squamous Cell Carcinoma Amenable for Surgical Resection. Clinical Cancer Research 2022, 28: 2796-2806. PMID: 35443062, DOI: 10.1158/1078-0432.ccr-21-3239.Peer-Reviewed Original ResearchOral squamous cell carcinomaProgression-free survivalSquamous cell carcinomaSurgical resectionCell carcinomaTreatment-related adverse event ratesAdvanced oral squamous cell carcinomaMajor pathologic response rateNeck squamous cell carcinomaPathologic response ratePlatinum-taxane chemotherapyCycles of chemotherapyAdverse event ratesMajor pathological responseExcellent clinical outcomesAddition of erlotinibCycles of treatmentPre-treatment samplesConcurrent erlotinibErlotinib armNeoadjuvant erlotinibInduction chemotherapyNeoadjuvant chemotherapySecondary endpointsDefinitive surgeryA general calculus of fitness landscapes finds genes under selection in cancers
Hsu TK, Asmussen J, Koire A, Choi BK, Gadhikar M, Huh E, Lin CH, Konecki D, Kim YW, Pickering C, Kimmel M, Donehower L, Frederick M, Myers JN, Katsonis P, Lichtarge O. A general calculus of fitness landscapes finds genes under selection in cancers. Genome Research 2022, 32: gr.275811.121. PMID: 35301263, PMCID: PMC9104707, DOI: 10.1101/gr.275811.121.Peer-Reviewed Original ResearchConceptsEvolution of traitsFitness landscapeGenotype-phenotype relationshipsEvolutionary relationshipsComplex traitsPositive selectionGenomic searchSpecific traitsCancer InsightsGenesGenetic variantsFunctional impactTraitsExperimental supportLandscapeVariantsPhenotypeEvolutionSelectionGenotypesCancer cohort