2024
Effects of gut microbiota on immune checkpoint inhibitors in multi-cancer and as microbial biomarkers for predicting therapeutic response
Lin Y, Xie M, Lau H, Zeng R, Zhang R, Wang L, Li Q, Wang Y, Chen D, Jiang L, Damsky W, Yu J. Effects of gut microbiota on immune checkpoint inhibitors in multi-cancer and as microbial biomarkers for predicting therapeutic response. Med 2024 PMID: 39515321, DOI: 10.1016/j.medj.2024.10.007.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsMicrobial biomarkersPredicting ICI responseGut microbiotaICI responseMulti-cancersEffects of gut microbiotaCheckpoint inhibitorsModulating CD8<sup>+</sup> T cells activityCD8<sup>+</sup> T cell activationICI respondersImmune checkpoint inhibitor recipientsPredictors of ICI responseImmune checkpoint inhibitor efficacyHungatella hathewayiCancer typesFecal metagenomesGut bacteriaSignature speciesT cell activationMicrobiota compositionF. prausnitziiPredicting therapeutic responseWilcoxon rank testMicrobiota
2023
Combinatorial 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 challengeSubsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Horowitch B, Lee D, Ding M, Martinez-Morilla S, Aung T, Ouerghi F, Wang X, Wei W, Damsky W, Sznol M, Kluger H, Rimm D, Ishizuka J. Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma. Clinical Cancer Research 2023, 29: 2908-2918. PMID: 37233452, PMCID: PMC10524955, DOI: 10.1158/1078-0432.ccr-23-0215.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHuman melanoma cell linesMelanoma cell linesPD-L1Validation cohortYale-New Haven HospitalCombination of ipilimumabPD-L1 markersImmune checkpoint blockadePD-L1 biomarkerNew Haven HospitalSTAT1 levelsCell linesWestern blot analysisCheckpoint inhibitorsCheckpoint blockadeClinical responseOverall survivalImproved survivalResistance of cancersMetastatic melanomaMelanoma responsePredict responseTreatment responseDistinct patterns
2019
Evaluating the role of the COX2/PGE2 pathway in anti-melanoma immunity.
Ferreira M, Krykbaeva I, Damsky W, Kluger H, Bosenberg M. Evaluating the role of the COX2/PGE2 pathway in anti-melanoma immunity. Journal Of Clinical Oncology 2019, 37: e14114-e14114. DOI: 10.1200/jco.2019.37.15_suppl.e14114.Peer-Reviewed Original ResearchC57BL6/J micePD-L1 upregulationT cell exhaustionTumor implantationJ miceCell exhaustionDay 7Male C57BL6/J miceCOX2/PGE2 pathwayDay 32Anti-melanoma immunityBreast cancer modelSafety of inhibitorsAttractive pharmacologic targetML/daySyngeneic cell linesCheckpoint inhibitorsPartial responseMelanoma patientsComplete regressionSafety profileMetastatic melanomaPathway blockadePGE2 pathwayCOX2 inhibitors
2016
A comprehensive system of congenic mouse melanoma models for evaluation of immune therapies
Bosenberg M, Meeth K, Damsky W. A comprehensive system of congenic mouse melanoma models for evaluation of immune therapies. The Journal Of Immunology 2016, 196: 144.19-144.19. DOI: 10.4049/jimmunol.196.supp.144.19.Peer-Reviewed Original ResearchImmune therapyMouse modelImmune systemImmune checkpoint inhibitorsSubset of patientsRenal cell carcinomaMouse melanoma modelMouse melanoma cell lineCheckpoint inhibitorsMelanoma cell linesMelanoma patientsCell carcinomaLung cancerCancer immunologyMalignant melanomaProstate cancerTherapeutic approachesMelanoma modelSkin cancerHuman melanomaTherapyTumor microenvironmentCancerFlow cytometryPatients