2024
PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy
Davies D, Kamdar S, Woolf R, Zlatareva I, Iannitto M, Morton C, Haque Y, Martin H, Biswas D, Ndagire S, Munonyara M, Gillett C, O’Neill O, Nussbaumer O, Hayday A, Wu Y. PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy. Nature Cancer 2024, 5: 420-432. PMID: 38172341, PMCID: PMC10965442, DOI: 10.1038/s43018-023-00690-0.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitionPD-1T cellsProgrammed cell death protein 1Cell death protein 1PD-1 expressionResponse to TCR signalingPD-1 engagementT cell recognitionCancer immunotherapyTCR signalingTranscriptomic programsProtein 1CancerFunctional relevanceCellsImmunotherapyNeoantigensMelanomaPatientsOncology
2021
Impact of cancer evolution on immune surveillance and checkpoint inhibitor response
Wu Y, Biswas D, Swanton C. Impact of cancer evolution on immune surveillance and checkpoint inhibitor response. Seminars In Cancer Biology 2021, 84: 89-102. PMID: 33631295, PMCID: PMC9253787, DOI: 10.1016/j.semcancer.2021.02.013.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsCheckpoint inhibitor therapyCheckpoint inhibitorsIntratumour heterogeneityImmune surveillancePatient's response to immune checkpoint inhibitorsResponse to immune checkpoint inhibitorsCheckpoint inhibitor responseProportion of patientsStandard of carePredictive biomarkersStratify patientsImmune evasionDiagnostic accuracyInhibitor responseImmune systemMechanisms of genetic instabilityPatientsGenetic instabilityCancer evolutionTherapyCancerSurveillanceInhibitorsIntratumourMeta-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
Metastasis and Immune Evasion from Extracellular cGAMP HydrolysisENPP1, a Therapeutic Target in Chromosomally Unstable Tumors
Li J, Duran M, Dhanota N, Chatila W, Bettigole S, Kwon J, Sriram R, Humphries M, Salto-Tellez M, James J, Hanna M, Melms J, Vallabhaneni S, Litchfield K, Usaite I, Biswas D, Bareja R, Li H, Martin M, Dorsaint P, Cavallo J, Li P, Pauli C, Gottesdiener L, DiPardo B, Hollmann T, Merghoub T, Wen H, Reis-Filho J, Riaz N, Su S, Kalbasi A, Vasan N, Powell S, Wolchok J, Elemento O, Swanton C, Shoushtari A, Parkes E, Izar B, Bakhoum S. Metastasis and Immune Evasion from Extracellular cGAMP HydrolysisENPP1, a Therapeutic Target in Chromosomally Unstable Tumors. Cancer Discovery 2020, 11: 1212-1227. PMID: 33372007, PMCID: PMC8102348, DOI: 10.1158/2159-8290.cd-20-0387.Peer-Reviewed Original ResearchConceptsChromosomally unstable tumorsAnti-PD-1/PD-L1 treatmentResponse to immune checkpoint blockadeReduced immune cell infiltrationUnstable tumorsGeneration of extracellular adenosineCancer cells to immune cellsImmune-suppressive pathwaysImmune checkpoint blockadeResistance to immunotherapyTumor immune infiltrationImmune cell infiltrationEvading immune surveillanceMetastatic cancer cellsCGAS-STING innate immune pathwayExtracellular cGAMPCheckpoint blockadeInnate immune pathwaysTumor inflammationImmune surveillanceExtracellular adenosineImmune infiltrationIncreased metastasisImmune cellsCell infiltrationPervasive chromosomal instability and karyotype order in tumour evolution
Watkins T, Lim E, Petkovic M, Elizalde S, Birkbak N, Wilson G, Moore D, Grönroos E, Rowan A, Dewhurst S, Demeulemeester J, Dentro S, Horswell S, Au L, Haase K, Escudero M, Rosenthal R, Bakir M, Xu H, Litchfield K, Lu W, Mourikis T, Dietzen M, Spain L, Cresswell G, Biswas D, Lamy P, Nordentoft I, Harbst K, Castro-Giner F, Yates L, Caramia F, Jaulin F, Vicier C, Tomlinson I, Brastianos P, Cho R, Bastian B, Dyrskjøt L, Jönsson G, Savas P, Loi S, Campbell P, Andre F, Luscombe N, Steeghs N, Tjan-Heijnen V, Szallasi Z, Turajlic S, Jamal-Hanjani M, Van Loo P, Bakhoum S, Schwarz R, McGranahan N, Swanton C. Pervasive chromosomal instability and karyotype order in tumour evolution. Nature 2020, 587: 126-132. PMID: 32879494, PMCID: PMC7611706, DOI: 10.1038/s41586-020-2698-6.Peer-Reviewed Original ResearchConceptsSomatic copy number alterationsWhole-genome doublingChromosomal instabilityHuman leukocyte antigenChromosomal instability resultsSomatic copy number alteration analysisLoss of chromosome 8pFocal somatic copy number alterationsLoss of heterozygosityCopy number alterationsMetastatic samplesTumor evolutionKaryotype remodelingChromosome 8q24.1Clear cell renal cellChromosome 1q21Evolutionary eventsHER2+ breast cancerChromosome 8pChromosome 11q13.3Focal amplificationHaploid copiesRecurrent lossSubclonal frequenciesClonal events