Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma. (R)-2-hydroxyglutarate generated by the mIDH1 enzyme inhibits multiple α-ketoglutarate–dependent enzymes, altering epigenetics and metabolism. Here, by developing mIDH1-driven genetically engineered mouse models, we show that mIDH1 supports cholangiocarcinoma tumor maintenance through an immunoevasion program centered on dual (R)-2-hydroxyglutarate–mediated mechanisms: suppression of CD8+ T-cell activity and tumor cell–autonomous inactivation of TET2 DNA demethylase. Pharmacologic mIDH1 inhibition stimulates CD8+ T-cell recruitment and interferon γ (IFNγ) expression and promotes TET2-dependent induction of IFNγ response genes in tumor cells. CD8+ T-cell depletion or tumor cell–specific ablation of TET2 or IFNγ receptor 1 causes treatment resistance. Whereas immune-checkpoint activation limits mIDH1 inhibitor efficacy, CTLA4 blockade overcomes immunosuppression, providing therapeutic synergy. The findings in this mouse model of cholangiocarcinoma demonstrate that immune function and the IFNγ–TET2 axis are essential for response to mIDH1 inhibition and suggest a novel strategy for potentiating efficacy. Significance: Mutant IDH1 inhibition stimulates cytotoxic T-cell function and derepression of the DNA demethylating enzyme TET2, which is required for tumor cells to respond to IFNγ. The discovery of mechanisms of treatment efficacy and the identification of synergy by combined CTLA4 blockade provide the foundation for new therapeutic strategies. See related commentary by Zhu and Kwong, p. 604. This article is highlighted in the In This Issue feature, p. 587

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The COVID-19 pandemic exerted complex pressures on the nephrology community. Despite multiple prior reviews on acute peritoneal dialysis during the pandemic, the effects of COVID-19 on maintenance peritoneal dialysis patients remain underexamined. This review synthesizes and reports findings from 29 total cases of chronic peritoneal dialysis patients with COVID-19, encompassing 3 case reports, 13 case series, and 13 cohort studies. When available, data for patients with COVID-19 on maintenance hemodialysis are also discussed. Finally, we present a chronological timeline of evidence regarding the presence of SARS-CoV-2 in spent peritoneal dialysate and explore trends in telehealth as they relate to peritoneal dialysis patients during the pandemic. We conclude that the COVID-19 pandemic has underscored the efficacy, flexibility, and utility of peritoneal dialysis.