Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024 PMID: 39561007, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine modelInvestigation of T cell phenotypes associated with response or resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC).
Kashima S, Ye Z, Meliki A, Hugaboom M, Schindler N, Graham J, Moritz V, El Ahmar N, Nabil Laimon Y, Canniff J, Saliby R, Lee G, Machaalani M, Sun M, Xu W, Signoretti S, McGregor B, McKay R, CHOUEIRI T, Braun D. Investigation of T cell phenotypes associated with response or resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC). Journal Of Clinical Oncology 2024, 42: 4515-4515. DOI: 10.1200/jco.2024.42.16_suppl.4515.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaCD8+ T cell infiltrationT cell infiltrationNon-respondersTumor microenvironmentT cellsRCC tumor microenvironmentResistance to immune checkpoint inhibitorsICI responseImmune checkpoint inhibitor treatmentImmune checkpoint inhibitor efficacyCD8+ T cellsExpressed PD-1ICI-treated patientsGene programGene signature scoresTumor mutation loadCellular compositionGene expression signaturesSingle-cell transcriptome analysisCheckpoint inhibitorsPD-1Partial responseSystemic therapySLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma
Wirth L, Hugaboom M, Street K, Ruthen N, Jegede O, Schindler N, McDermott D, Plimack E, Sosman J, Haas N, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. SLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma. The Journal Of Immunology 2024, 212: 1491_5876-1491_5876. DOI: 10.4049/jimmunol.212.supp.1491.5876.Peer-Reviewed Original ResearchCD8+ T cellsImmune-checkpoint inhibitorsRenal cell carcinomaCD8+ T-cell effector functionT cell effector functionT cellsCell carcinomaResistance to immune-checkpoint inhibitorsEffector functionsPopulation of CD8+ T cellsCD3+ T cellsTreatment of renal cell carcinomaHealthy human PBMCTumor-infiltrating lymphocytesAnti-tumor responsesPatient T cellsReduction of pro-inflammatory cytokinesAnti-tumor functionPro-inflammatory cytokinesSingle-cell transcriptome analysisNivolumab monotherapySLAMF7 expressionClinical benefitGranzyme BIFN-g