BACKGROUND & AIMS:The pathogenesis of immune checkpoint inhibitor (ICI)-colitis remains incompletely understood. We sought to identify key cellular drivers of ICI-colitis and their similarities to idiopathic ulcerative colitis, and to determine potential novel therapeutic targets. METHODS: We used a cross-sectional approach to study patients with ICI-colitis, those receiving ICI without the development of colitis, idiopathic ulcerative colitis, and healthy controls. A subset of patients with ICI-colitis were studied longitudinally. We applied a range of methods, including multiparameter and spectral flow cytometry, spectral immunofluorescence microscopy, targeted gene panels, and bulk and single-cell RNA sequencing. RESULTS: We demonstrate CD8 þ tissue resident memory T (T RM ) cells are the dominant activated T cell subset in ICIcolitis. The pattern of gastrointestinal immunopathology is distinct from ulcerative colitis at both the immune and Gastroenterology 2021;161:1229-1244 BASIC AND TRANSLATIONAL AT epithelial-signaling levels. CD8 þ T RM cell activation correlates with clinical and endoscopic ICI-colitis severity. Single-cell RNA sequencing analysis confirms activated CD8 þ T RM cells express high levels of transcripts for checkpoint inhibitors and interferon-gamma in ICI-colitis. We demonstrate similar findings in both anti-CTLA-4/PD-1 combination therapy and in anti-PD-1 inhibitor-associated colitis. On the basis of our data, we successfully targeted this pathway in a patient with refractory ICIcolitis, using the JAK inhibitor tofacitinib. CONCLUSIONS: Interferon gamma-producing CD8 þ T RM cells are a pathological hallmark of ICI-colitis and a novel target for therapy.

Innovative educational strategies can provide variety and enhance student learning while addressing complex logistical and financial issues facing modern anatomy education. Observe-Reflect-Draw-Edit-Repeat (ORDER), a novel cyclical artistic process, has been designed based on cognitivist and constructivist learning theories, and on processes of critical observation, reflection and drawing in anatomy learning. ORDER was initially investigated in the context of a compulsory first year surface anatomy practical (ORDER-SAP) at a United Kingdom medical school in which a cross-over trial with pre-post anatomy knowledge testing was utilized and student perceptions were identified. Despite positive perceptions of ORDER-SAP, medical student (n = 154) pre-post knowledge test scores were significantly greater (P < 0.001) with standard anatomy learning methods (3.26, SD = ±2.25) than with ORDER-SAP (2.17, ±2.30). Based on these findings, ORDER was modified and evaluated in the context of an optional self-directed gross anatomy online interactive tutorial (ORDER-IT) for participating first year medical students (n = 55). Student performance was significantly greater (P < 0.001) with ORDER-IT (2.71 ± 2.17) when compared to a control tutorial (1.31 ± 2.03). Performances of students with visual and artistic preferences when using ORDER were not significantly different (P > 0.05) to those students without these characteristics. These findings will be of value to anatomy instructors seeking to engage students from diverse learning backgrounds in a research-led, innovative, time and cost-effective learning method, in the context of contrasting learning environments. Anat Sci Educ 10: 7-22. © 2016 American Association of Anatomists.