Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes
Sundar R, Chia D, Zhao J, Lee A, Kim G, Tan H, Pang A, Shabbir A, Willaert W, Ma H, Huang K, Hagihara T, Tan A, Ong C, Wong J, Seo C, Walsh R, Chan G, Cheo S, Soh C, Callebout E, Geboes K, Ng M, Lum J, Leow W, Selvarajan S, Hoorens A, Ang W, Pang H, Tan P, Yong W, Chia C, Ceelen W, So J. Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes. ESMO Open 2024, 9: 103681. PMID: 39288528, PMCID: PMC11421236, DOI: 10.1016/j.esmoop.2024.103681.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisPeritoneal cancer indexNivolumab combinationPeritoneal metastasisPeritoneal tumorsNaive CD8+ T cellsCD8+ central memoryEnhanced T cell infiltrationTreatment-related adverse eventsCD8+ T cellsGrade 4 vomitingRegression grade 1First-in-human trialImmune checkpoint inhibitionMemory CD4+T cell infiltrationImmunogenic cell deathSystemic immunotherapyCheckpoint inhibitionSystemic therapyCancer indexCD4+Intraperitoneal treatmentT cellsAdverse eventsEpigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Sundar R, Huang K, Kumar V, Ramnarayanan K, Demircioglu D, Her Z, Ong X, Bin Adam Isa Z, Xing M, Tan A, Tai D, Choo S, Zhai W, Lim J, Thakur M, Molinero L, Cha E, Fasso M, Niger M, Pietrantonio F, Lee J, Jeyasekharan A, Qamra A, Patnala R, Fabritius A, De Simone M, Yeong J, Ng C, Rha S, Narita Y, Muro K, Guo Y, Skanderup A, So J, Yong W, Chen Q, Göke J, Tan P. Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition. Gut 2021, 71: 1277-1288. PMID: 34433583, PMCID: PMC9185816, DOI: 10.1136/gutjnl-2021-324420.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionImmune microenvironmentHuman immune systemCheckpoint inhibitionActive human immune systemGastric cancerHuman T-cell infiltrationT cell cytolytic activityResistance to immune checkpoint inhibitionImmune systemProgression-free survivalImmunotherapy-treated patientsT cell infiltrationTumor immune microenvironmentT cell proportionsImmune-editingImmunotherapy resistanceFunctional in vivo studiesTumor kineticsHumanised miceAlternative promoter useTumor microenvironmentTherapeutic responseCytolytic activityImmune depletion