Dysregulation of CD4⁺ and CD8⁺ resident memory T, myeloid, and stromal cells in steroid-experienced, checkpoint inhibitor colitis.

ABSTRACT:

Background

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.

Methods

Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations.

Results

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 c

SUBMITTER: He JY 

PROVIDER: S-EPMC11033653 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature