Molly Fisher Thomas, Kamil Slowikowski, Kasidet Manakongtreecheep, Pritha Sen, Nandini Samanta, Jessica Tantivit, Mazen Nasrallah, Leyre Zubiri, Neal P Smith, Alice Tirard, Swetha Ramesh, Benjamin Y Arnold, Linda T Nieman, Jonathan H Chen, Thomas Eisenhaure, Karin Pelka, Yuhui Song, Katherine H Xu, Vjola Jorgji, Christopher J Pinto, Tatyana Sharova, Rachel Glasser, PuiYee Chan, Ryan J Sullivan, Hamed Khalili, Dejan Juric, Genevieve M Boland, Michael Dougan, Nir Hacohen, Bo Li, Kerry L Reynolds, Alexandra-Chloé Villani
Immune checkpoint inhibitor (ICI) therapy has revolutionized oncology, but treatments are limited by immune-related adverse events, including checkpoint inhibitor colitis (irColitis). Little is understood about the pathogenic mechanisms driving irColitis, which does not readily occur in model organisms, such as mice. To define molecular drivers of irColitis, we used single-cell multi-omics to profile approximately 300,000 cells from the colon mucosa and blood of 13 patients with cancer who developed irColitis (nine on anti-PD-1 or anti-CTLA-4 monotherapy and four on dual ICI therapy; most patients had skin or lung cancer), eight controls on ICI therapy and eight healthy controls...
May 9, 2024: Nature Medicine