2023
Manipulating mitochondrial electron flow enhances tumor immunogenicity
Mangalhara K, Varanasi S, Johnson M, Burns M, Rojas G, Esparza Moltó P, Sainz A, Tadepalle N, Abbott K, Mendiratta G, Chen D, Farsakoglu Y, Kunchok T, Hoffmann F, Parisi B, Rincon M, Vander Heiden M, Bosenberg M, Hargreaves D, Kaech S, Shadel G. Manipulating mitochondrial electron flow enhances tumor immunogenicity. Science 2023, 381: 1316-1323. PMID: 37733872, PMCID: PMC11034774, DOI: 10.1126/science.abq1053.Peer-Reviewed Original ResearchConceptsElectron transport chainMethylation-controlled J proteinMitochondrial electron transport chainElectron flowMitochondrial electron flowJ-proteinsEpigenetic activationTransport chainMitochondrial respirationTumor growthPresentation genesElectron entryNoncancer cellsMelanoma tumor growthCommon mechanismTherapeutic potentialGenesRelative contributionProteinGrowthKnockoutAntigen presentationRespirationT cell-mediated killingExpressionCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeMouse models for immuno-oncology
Bosenberg M, Liu E, Yu C, Palucka K. Mouse models for immuno-oncology. Trends In Cancer 2023, 9: 578-590. PMID: 37087398, DOI: 10.1016/j.trecan.2023.03.009.Peer-Reviewed Original Research
2020
IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy
Zhou T, Damsky W, Weizman OE, McGeary MK, Hartmann KP, Rosen CE, Fischer S, Jackson R, Flavell RA, Wang J, Sanmamed MF, Bosenberg MW, Ring AM. IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature 2020, 583: 609-614. PMID: 32581358, PMCID: PMC7381364, DOI: 10.1038/s41586-020-2422-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDisease Models, AnimalFemaleHepatocyte Nuclear Factor 1-alphaHistocompatibility Antigens Class IHumansImmunotherapyIntercellular Signaling Peptides and ProteinsInterleukin-18Kaplan-Meier EstimateKiller Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsReceptors, Interleukin-18Stem CellsTumor MicroenvironmentConceptsIL-18IL-18BPT cellsAnti-PD-1 resistant tumorsWild-type IL-18Potent anti-tumor effectsMajor histocompatibility complex class IIL-18 pathwayIL-18 therapyInterleukin-18 pathwayMajor therapeutic barrierStem-like TCF1Anti-tumor immunityTumor-infiltrating lymphocytesNatural killer cellsRecombinant IL-18Histocompatibility complex class IAnti-tumor effectsComplex class IAnti-tumor activityMouse tumor modelsModern immunotherapyPrecursor CD8Effector CD8Exhausted CD8