2022
Resistance to systemic immune checkpoint inhibition in the peritoneal niche
Chia D, Gwee Y, Sundar R. Resistance to systemic immune checkpoint inhibition in the peritoneal niche. Journal For ImmunoTherapy Of Cancer 2022, 10: e004749. PMID: 35728873, PMCID: PMC9214396, DOI: 10.1136/jitc-2022-004749.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionResistance to immune checkpoint inhibitionPeritoneal metastasisCheckpoint inhibitionMetastatic nicheResponse to ICIImmune checkpoint inhibition therapySensitive to immune checkpoint inhibitionIntrinsic tumor factorsPresence of ascitesDeficient mismatch repairPeritoneal microenvironmentTumor factorsMalignant ascitesPrimary resistanceClinical entityTherapeutic optionsMicrosatellite instable tumorsPeritoneal cavityGastrointestinal cancerParacrine factorsAscitesConcurrent ascitesPatientsInstable tumors
2021
Epigenetic 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
2019
Epigenetic alternate promoter utilization and association with PD-L1 expression in Epstein–Barr virus positive gastric cancer.
Sundar R, Qamra A, Tan A, Zhang S, Ng C, Teh B, Lee J, Kim K, Tan P. Epigenetic alternate promoter utilization and association with PD-L1 expression in Epstein–Barr virus positive gastric cancer. Journal Of Clinical Oncology 2019, 37: e15509-e15509. DOI: 10.1200/jco.2019.37.15_suppl.e15509.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1Gastric cancerEBV-negativeAnti-PD-1 immune checkpoint inhibitorsEBV-encoded RNA in situ hybridizationImmune-evasionProtein expression of PD-L1PD-L1 transcript expressionExpression of PD-L1Resistance to immune checkpoint inhibitionEpstein-Barr virus-positive gastric cancerEpstein-Barr virus-associated gastric cancerImmune checkpoint inhibitionImmune checkpoint inhibitorsPD-L1 immunohistochemistryPrimary tumor resectionPositive gastric cancerGastric cancer patientsEBV-negative samplesSamsung Medical CentreRNA in situ hybridizationCheckpoint inhibitorsCheckpoint inhibitionEBV statusEpigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer
Sundar R, Huang K, Qamra A, Kim K, Kim S, Kang W, Tan A, Lee J, Tan P. Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer. Annals Of Oncology 2019, 30: 424-430. PMID: 30624548, PMCID: PMC6442650, DOI: 10.1093/annonc/mdy550.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionMetastatic gastric cancerT cell cytolytic activityResistance to immune checkpoint inhibitionCheckpoint inhibitionGastric cancerCytolytic activityImmune evasionMedian progression-free survivalPhase II clinical trial of patientsCancer treated with immunotherapyClinical trials of patientsMechanisms of immune evasionResponse rateTreated with pembrolizumabPhase II clinical trialProgression-free survivalFresh tumor biopsiesPost-treatment biopsiesCohort of patientsTrial of patientsEarly gastric cancerArchival tissue samplesClinical responseTumor biopsies