2023
Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCarcinoma, Renal CellHepatitis A Virus Cellular Receptor 2HumansImmune System DiseasesKidney NeoplasmsMedical OncologyTumor MicroenvironmentConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samplesLeveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies
Anderson K, Braun D, Buqué A, Gitto S, Guerriero J, Horton B, Keenan B, Kim T, Overacre-Delgoffe A, Ruella M, Triplett T, Veeranki O, Verma V, Zhang F. Leveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies. Journal For ImmunoTherapy Of Cancer 2023, 11: e006533. PMID: 37399356, PMCID: PMC10314654, DOI: 10.1136/jitc-2022-006533.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune resistance mechanismsImmune resistanceChimeric antigen receptor T cellsAntigen receptor T cellsImmune checkpoint inhibitorsReceptor T cellsVariety of malignanciesNew therapeutic strategiesResistance mechanismsCheckpoint inhibitorsDurable responsesMost patientsAnticancer immunotherapyTherapy combinationsCurrent therapiesT cellsIndividual patientsSolid cancersTherapeutic strategiesTumor profilingPatientsOverall efficacySuppressive mechanismsBispecific antibodiesTumor microenvironment
2022
Landscape of helper and regulatory antitumour CD4+ T cells in melanoma
Oliveira G, Stromhaug K, Cieri N, Iorgulescu J, Klaeger S, Wolff J, Rachimi S, Chea V, Krause K, Freeman S, Zhang W, Li S, Braun D, Neuberg D, Carr S, Livak K, Frederick D, Fritsch E, Wind-Rotolo M, Hacohen N, Sade-Feldman M, Yoon C, Keskin D, Ott P, Rodig S, Boland G, Wu C. Landscape of helper and regulatory antitumour CD4+ T cells in melanoma. Nature 2022, 605: 532-538. PMID: 35508657, PMCID: PMC9815755, DOI: 10.1038/s41586-022-04682-5.Peer-Reviewed Original ResearchMeSH KeywordsAntigen-Presenting CellsAntigens, NeoplasmCD4-Positive T-LymphocytesHLA AntigensHumansMelanomaPhenotypeSkin NeoplasmsTumor Cells, CulturedTumor MicroenvironmentConceptsHLA class IIT cellsClass IIHLA classImmune evasionHuman leukocyte antigen class IIMelanoma specimensClass II positivityTumor-reactive CD4T regulatory (Treg) cellsAntigen-presenting cellsTumor-associated antigensHLA class IHuman melanoma specimensRecognition of antigenAntitumour responseImmunosuppressive CD4Treg clonesTreg cellsRegulatory cellsCytotoxic CD4Neoantigen loadTumor antigensCD4Tumor microenvironment
2021
Progressive immune dysfunction with advancing disease stage in renal cell carcinoma
Braun DA, Street K, Burke KP, Cookmeyer DL, Denize T, Pedersen CB, Gohil SH, Schindler N, Pomerance L, Hirsch L, Bakouny Z, Hou Y, Forman J, Huang T, Li S, Cui A, Keskin DB, Steinharter J, Bouchard G, Sun M, Pimenta EM, Xu W, Mahoney KM, McGregor BA, Hirsch MS, Chang SL, Livak KJ, McDermott DF, Shukla SA, Olsen LR, Signoretti S, Sharpe AH, Irizarry RA, Choueiri TK, Wu CJ. Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell 2021, 39: 632-648.e8. PMID: 33711273, PMCID: PMC8138872, DOI: 10.1016/j.ccell.2021.02.013.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaM2-like macrophagesRenal cell carcinomaAdvanced diseaseExhausted CD8Cell carcinomaDisease stageAdvanced/metastaticImmune inhibitory pathwaysProgressive immune dysfunctionCell renal cell carcinomaAdjacent non-tumor tissuesTumor immune microenvironmentPro-inflammatory macrophagesM2-like polarizationNon-tumor tissuesMetastatic diseaseImmune dysfunctionWorse prognosisImmune microenvironmentImmune cellsCell dysfunctionExternal cohortInhibitory pathwaysMyeloid compartment