biostudies-literatureHe JYParker Institute for Cancer ImmunotherapyKenneth Rainin FoundationCrohn’s and Colitis FoundationNIDDK NIH HHSBurroughs Wellcome FundNIAID NIH HHSNCI NIH HHSNational Institutes of HealthUCSF ImmunoXV Foundation for Cancer ResearchDamon Runyon Cancer Research Foundatione008628https://www.ebi.ac.uk/biostudies/studies/S-EPMC11033653biostudies-literatureUnknown12(4)<h4>Background</h4>Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear.<h4>Methods</h4>Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations.<h4>Results</h4>CPI colitis biopsies showed enrichment of CD4⁺resident memory (RM) T cells in addition to CD8⁺ RM and cytotoxic CD8⁺ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38⁺ HLA-DR⁺ CD4⁺ RM and cytotoxic CD8⁺ T cJournal for immunotherapy of cancerDysregulation of CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; resident memory T, myeloid, and stromal cells in steroid-experienced, checkpoint inhibitor colitis.PMC11033653N/AK08AI139375K08 DK123202T2023-011R35 CA253175Career Award for Medical ScientistsCoPilot AwardCI 110-21K08 AI139375K08DK123202KRA000152Career Development AwardYang HBain JPisco AOZhang LCombes AJFong LShi YLaw KFan FMennillo EShen AOh DYDavidson BHe JYKim YJRao AAKattah MGKushnoor DRusu ICheung AAndersen CTsui JfalseDysregulation of CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; resident memory T, myeloid, and stromal cells in steroid-experienced, checkpoint inhibitor colitis.<h4>Background</h4>Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear.<h4>Methods</h4>Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations.<h4>Results</h4>CPI colitis biopsies showed enrichment of CD4⁺resident memory (RM) T cells in addition to CD8⁺ RM and cytotoxic CD8⁺ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38⁺ HLA-DR⁺ CD4⁺ RM and cytotoxic CD8⁺ T c2024-01-01T00:00:00Z2024 Apr2026-06-08T06:04:15.744Z2026-06-08T03:14:26.326ZS-EPMC110336533864293810.1136/jitc-2023-008628