2022
Abstract 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
2021
Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition
Litchfield K, Reading J, Puttick C, Thakkar K, Abbosh C, Bentham R, Watkins T, Rosenthal R, Biswas D, Rowan A, Lim E, Al Bakir M, Turati V, Guerra-Assunção J, Conde L, Furness A, Saini S, Hadrup S, Herrero J, Lee S, Van Loo P, Enver T, Larkin J, Hellmann M, Turajlic S, Quezada S, McGranahan N, Swanton C. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell 2021, 184: 596-614.e14. PMID: 33508232, PMCID: PMC7933824, DOI: 10.1016/j.cell.2021.01.002.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCD8 AntigensChemokine CXCL13Chromosomes, Human, Pair 9Cohort StudiesCyclin D1DNA Copy Number VariationsExomeGene AmplificationHumansImmune Checkpoint InhibitorsImmune EvasionMultivariate AnalysisMutationNeoplasmsPolymorphism, Single NucleotideReceptors, CCR5T-LymphocytesTumor BurdenConceptsTumor mutational burdenTumor-infiltrating lymphocytesHistocompatibility leukocyte antigenCheckpoint inhibitorsCD8 tumor-infiltrating lymphocytesCPI-treated patientsTumor cell-intrinsicClinical outcome criteriaCopy-number analysisCXCL9 expressionCCND1 amplificationMutational burdenLeukocyte antigenTumor typesMultivariate predictorsSingle-cell RNA sequencingAdaptive immunityAssociated with resistanceWhole exomeMicroenvironmental featuresOutcome criteriaCopy-numberFunctional evidenceRNA-seqTumor
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