Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy
By Jérôme C. Martin, Christie Chang, G. Boschetti, R. Ungaro, M. Giri, J. Grout, K. Gettler, Ling-shiang Chuang, Shikha Nayar, A. Greenstein and 21 more. Cell, 2019
691 citations recorded by the source corpus.
SUMMARY Clinical benefits of cytokine blockade in ileal Crohn’s disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.
Subfields: Genetics, Immunology
View Paper: https://www.semanticscholar.org/paper/56f93073e97a7ad471a0c3bc027400a8d011642c
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In Genetics
Citations in the corpus
- Deciphering cell–cell interactions and communication from gene expression (2020, methodology): “Although this method can be applied to bulk data, microdissected or single-cell data sets are preferred as they capture the full heterogeneity of expression across cells 19,48,49,55,60,62 , resulting in clearer differences in expression 92 .”
- TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment (2022, background): “Due to the striking genetic and cellular heterogeneity within the TME, only a fraction of patients could benefit from immunotherapy (5,6).”
- Spatiotemporal analysis of human intestinal development at single-cell resolution (2021, positive): “The final cluster expressedKIT highlighting it as a ILC cell which together withKLRB1,RORC and ID2 demonstrated this to be of the ILC-3 subtype (Martin et al., 2019).”