Featured Publications
A clonal expression biomarker associates with lung cancer mortality
Biswas D, Birkbak N, Rosenthal R, Hiley C, Lim E, Papp K, Boeing S, Krzystanek M, Djureinovic D, La Fleur L, Greco M, Döme B, Fillinger J, Brunnström H, Wu Y, Moore D, Skrzypski M, Abbosh C, Litchfield K, Al Bakir M, Watkins T, Veeriah S, Wilson G, Jamal-Hanjani M, Moldvay J, Botling J, Chinnaiyan A, Micke P, Hackshaw A, Bartek J, Csabai I, Szallasi Z, Herrero J, McGranahan N, Swanton C. A clonal expression biomarker associates with lung cancer mortality. Nature Medicine 2019, 25: 1540-1548. PMID: 31591602, PMCID: PMC6984959, DOI: 10.1038/s41591-019-0595-z.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerClinicopathological risk factorsCell lung cancerLung cancer mortalityPrognostic gene expression signaturesCancer cell proliferationGene expression signaturesCancer mortalityLung cancerRisk factorsExpression-based biomarkersCopy number gainsDisease subtypesClinical descriptorsTranscriptomic biomarkersIndividual tumorsCancer typesDiagnostic precisionMolecular biomarkersExpression signaturesCell proliferationDNA copy number gainsBiomarkersPatientsIntratumor heterogeneityA local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer
Wu Y, Biswas D, Usaite I, Angelova M, Boeing S, Karasaki T, Veeriah S, Czyzewska-Khan J, Morton C, Joseph M, Hessey S, Reading J, Georgiou A, Al-Bakir M, McGranahan N, Jamal-Hanjani M, Hackshaw A, Quezada S, Hayday A, Swanton C. A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer. Nature Cancer 2022, 3: 696-709. PMID: 35637401, PMCID: PMC9236901, DOI: 10.1038/s43018-022-00376-z.Peer-Reviewed Original ResearchConceptsT cell populationsT cellsLung tissueLung cancerCD8+ T cellsNonsmall-cell lung cancerNonsmall cell lung cancerEffector memory phenotypeT cell compartmentCell lung cancerAssociated with survivalNonmalignant lung tissuesStem-like featuresNontumor lung tissuesT cell biologyHuman lung tissueImmunotherapeutic strategiesMemory phenotypeNatural killerLung tumorsTissue-residentPost-surgeryResident memoryMurine tissuesTumor
2023
Abstract LB237: Functional characterisation of TRACERx reveals mechanisms of NSCLC evolution
Lu W, Zalmas L, Bailey C, Pich O, Ruiz C, Black J, Stavrou G, Biswas D, Gimeno-Valiente F, Litchfield K, Bartek J, McGranahan N, Kanu N, Swanton C. Abstract LB237: Functional characterisation of TRACERx reveals mechanisms of NSCLC evolution. Cancer Research 2023, 83: lb237-lb237. DOI: 10.1158/1538-7445.am2023-lb237.Peer-Reviewed Original ResearchNon-small cell lung cancerElevated chromosomal instabilityWhole-genome doublingChromosomal instabilityIntratumoral heterogeneityHomologous recombination repairDNA damage responseAmerican Association for Cancer Research annual meetingsPC9 cellsRates of acquired resistanceIncreased intratumoral heterogeneityCell lung cancerIncreased CINDrug-resistant tumorsGenome doublingFunctional characterisationStructural chromosome instabilityWhole-genome doubling eventsFAT1 mutationsHomologous recombination repair pathwayBRCA1 foci formationChromosomal gainsMitotic error rateTargeted therapySolid tumorsThe evolution of lung cancer and impact of subclonal selection in TRACERx
Frankell A, Dietzen M, Al Bakir M, Lim E, Karasaki T, Ward S, Veeriah S, Colliver E, Huebner A, Bunkum A, Hill M, Grigoriadis K, Moore D, Black J, Liu W, Thol K, Pich O, Watkins T, Naceur-Lombardelli C, Cook D, Salgado R, Wilson G, Bailey C, Angelova M, Bentham R, Martínez-Ruiz C, Abbosh C, Nicholson A, Le Quesne J, Biswas D, Rosenthal R, Puttick C, Hessey S, Lee C, Prymas P, Toncheva A, Smith J, Xing W, Nicod J, Price G, Kerr K, Naidu B, Middleton G, Blyth K, Fennell D, Forster M, Lee S, Falzon M, Hewish M, Shackcloth M, Lim E, Benafif S, Russell P, Boleti E, Krebs M, Lester J, Papadatos-Pastos D, Ahmad T, Thakrar R, Lawrence D, Navani N, Janes S, Dive C, Blackhall F, Summers Y, Cave J, Marafioti T, Herrero J, Quezada S, Peggs K, Schwarz R, Van Loo P, Miedema D, Birkbak N, Hiley C, Hackshaw A, Zaccaria S, Jamal-Hanjani M, McGranahan N, Swanton C. The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature 2023, 616: 525-533. PMID: 37046096, PMCID: PMC10115649, DOI: 10.1038/s41586-023-05783-5.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerDisease-free survivalCell lung cancerWhole-genome doublingLung cancerLung adenocarcinomaAssociated with shorter disease-free survivalShorter disease-free survivalEvolution of lung cancerPattern of relapseSubclonal selectionPrimary study endpointHistory of smokingSubclonal expansionsCopy number instabilityEGFR mutationsCancer-associated mortalityCopy number heterogeneityClinical outcomesStudy endpointIntratumour heterogeneityNever-smokersClonal expansionFollow-upOncogenic isoform
2022
Abstract 5636: V-delta-1 T cells are resident in the human lung and associate with survival in patients with non-small cell lung cancer in the TRACERx Study
Wu Y, Biswas D, Usaite I, Mihaela A, Boeing S, Karasaki T, Veeriah S, Czyzewska-Khan J, Reading J, Georgiou A, Al-Bakir M, McGranahan N, Jamal-Hanjani M, Hackshaw A, Consortium T, Quezada S, Hayday A, Swanton C. Abstract 5636: V-delta-1 T cells are resident in the human lung and associate with survival in patients with non-small cell lung cancer in the TRACERx Study. Cancer Research 2022, 82: 5636-5636. DOI: 10.1158/1538-7445.am2022-5636.Peer-Reviewed Original ResearchNon-small cell lung cancerCell lung cancerT cell compartmentV delta 1T cellsAssociated with survivalLung cancerTRACERx studyLung tissueAmerican Association for Cancer Research annual meetingsStage I-III non-small cell lung cancerT cell knockout miceCD8+ T cellsMurine tissuesFirst-in-human clinical trialIL-17-producingNon-malignant lung tissueT-cell immunotherapyT-cell receptor sequencingT cell clonesIL-17 productionT helper 1Acute myeloid leukemiaSusceptibility to carcinogenesisHuman lungAbstract 645: Heterogeneity of immunotherapy biomarkers in the TRACERx non-small cell lung cancer multi-region lung cancer cohort study
Hiley C, Litchfield K, Pich O, Moore D, Naceur-Lombardelli C, Veeriah S, Bakir M, Summan S, Grigoriadis K, Ruiz C, Puttick C, Enfield K, Ward S, Frankell A, Biswas D, Rosenthal R, Birkbak N, Jamal-Hanjani M, McGranahan N, Swanton C, Consortium T. Abstract 645: Heterogeneity of immunotherapy biomarkers in the TRACERx non-small cell lung cancer multi-region lung cancer cohort study. Cancer Research 2022, 82: 645-645. DOI: 10.1158/1538-7445.am2022-645.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor mutational burdenIntra-tumor heterogeneityIntratumoral heterogeneityCancer Cohort StudyImmunotherapy biomarkersTumor regionAmerican Association for Cancer Research annual meetingsPredictors of response to immunotherapyCohort studyPrediction of immunotherapy responseTumor purityNeo-adjuvant settingResponse to immunotherapyFirst-line therapyImpact of intratumoral heterogeneityCell lung cancerMisclassification of patientsWhole-exome sequencingHeterogeneity of expressionMetastatic settingPDL1 immunohistochemistryPrimary tumorImmunotherapy responseMutational burden
2020
The T cell differentiation landscape is shaped by tumour mutations in lung cancer
Ghorani E, Reading J, Henry J, Massy M, Rosenthal R, Turati V, Joshi K, Furness A, Ben Aissa A, Saini S, Ramskov S, Georgiou A, Sunderland M, Wong Y, Mucha M, Day W, Galvez-Cancino F, Becker P, Uddin I, Oakes T, Ismail M, Ronel T, Woolston A, Jamal-Hanjani M, Veeriah S, Birkbak N, Wilson G, Litchfield K, Conde L, Guerra-Assunção J, Blighe K, Biswas D, Salgado R, Lund T, Bakir M, Moore D, Hiley C, Loi S, Sun Y, Yuan Y, AbdulJabbar K, Turajilic S, Herrero J, Enver T, Hadrup S, Hackshaw A, Peggs K, McGranahan N, Chain B, Swanton C, Quezada S. The T cell differentiation landscape is shaped by tumour mutations in lung cancer. Nature Cancer 2020, 1: 546-561. PMID: 32803172, PMCID: PMC7115931, DOI: 10.1038/s43018-020-0066-y.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor mutational burdenT cellsUntreated non-small cell lung cancerLung cancerCD8 T cell differentiationHigh-dimensional flow cytometryAssociated with poor survivalPersistent antigen exposureCD8 T cellsCD4 T cellsCell lung cancerT cell functionT cell differentiationImmunotherapy outcomesTumor neoantigensUntreated tumorsMutational burdenAntigen exposureTumor mutationsPoor survivalCancer cohortGene signatureTherapeutic manipulationFlow cytometry
2019
5O Using single cell data to validate the cellular origins of a clonal expression biomarker in lung cancer
Biswas D, Birkbak N, McGranahan N, Swanton C. 5O Using single cell data to validate the cellular origins of a clonal expression biomarker in lung cancer. Annals Of Oncology 2019, 30: vii2. DOI: 10.1093/annonc/mdz413.010.Peer-Reviewed Original ResearchNon-small cell lung cancerBreast Cancer Research FoundationTumor sampling biasUniversity College London HospitalGene expression signaturesLung cancerChromosomal instabilityPrognostic gene expression signaturesCancer typesExpression signaturesProstate Cancer FoundationClinicopathological risk factorsCell lung cancerCopy-number gainsAssociated with survivalNIHR BRCIntra-tumor heterogeneityPredictive of outcomeExperimental Cancer Medicine CentreLondon HospitalLung Cancer CentreCancer Research UKCancer cell proliferationSingle-cell dataRNA sequencing data