Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism
Eguren-Santamaría I, Rodríguez I, Herrero-Martin C, de Piérola E, Azpilikueta A, Sánchez-Gregorio S, Bolaños E, Gomis G, Molero-Glez P, Chacón E, Mínguez J, Chiva S, Diez-Caballero F, de Andrea C, Teijeira Á, Sanmamed M, Melero I. Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism. OncoImmunology 2024, 13: 2373519. PMID: 38988823, PMCID: PMC11236292, DOI: 10.1080/2162402x.2024.2373519.Peer-Reviewed Original ResearchConceptsTumor fragmentsImmunotherapy combinationsIFNg productionActivation markersClinical response to PD-1 blockadeResponse to PD-1 blockadeAgonistic anti-CD137 mAbAnti-PD-1 treatmentAnti-CD137 mAbAnti-PD-1PD-1 blockadeSyngeneic immunocompetent miceInfiltrating T cellsShort-term cultureUnmet medical needAnti-CD137Contralateral tumorsBilateral tumorsCancer immunotherapyTissue culture supernatantsImmunocompetent miceSolid malignanciesT cellsMAb combinationsMouse tumorsUp-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulatedSequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial
Ascierto P, Casula M, Bulgarelli J, Pisano M, Piccinini C, Piccin L, Cossu A, Mandalà M, Ferrucci P, Guidoboni M, Rutkowski P, Ferraresi V, Arance A, Guida M, Maiello E, Gogas H, Richtig E, Fierro M, Lebbe C, Helgadottir H, Queirolo P, Spagnolo F, Tucci M, Del Vecchio M, Cao M, Minisini A, De Placido S, Sanmamed M, Mallardo D, Paone M, Vitale M, Melero I, Grimaldi A, Giannarelli D, Dummer R, Sileni V, Palmieri G. Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial. Nature Communications 2024, 15: 146. PMID: 38167503, PMCID: PMC10761671, DOI: 10.1038/s41467-023-44475-6.Peer-Reviewed Original ResearchConceptsOverall survivalSurvival outcomesNoncomparative phase II trialTotal progression-free survivalLong-term survival outcomesMEK inhibitionBRAF/MEK inhibitionFirst-line treatment approachFirst-line treatment optionBRAF/MEK inhibitorsT-lymphocyte antigen-4Cell death protein 1BRAFV600-mutant melanomaDual checkpoint blockadeFirst-line immunotherapyMetastatic BRAF V600Serum interferon gammaPhase II trialProgression-free survivalDeath protein 1BRAFV600-mutant metastatic melanomaLow baseline levelsBiomarker analysisCombination BRAFSequential immunotherapy