Your browser doesn't support javascript.
loading
Dysregulation of CD4+ and CD8+ resident memory T, myeloid, and stromal cells in steroid-experienced, checkpoint inhibitor colitis.
He, Jun Yan; Kim, Yang-Joon; Mennillo, Elvira; Rusu, Iulia; Bain, Jared; Rao, Arjun A; Andersen, Christopher; Law, Karen; Yang, Hai; Tsui, Jessica; Shen, Alan; Davidson, Brittany; Kushnoor, Divyashree; Shi, Yimin; Fan, Frances; Cheung, Alexander; Zhang, Li; Fong, Lawrence; Combes, Alexis J; Pisco, Angela O; Kattah, Michael G; Oh, David Y.
Afiliación
  • He JY; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Kim YJ; Chan Zuckerberg Biohub, San Francisco, California, USA.
  • Mennillo E; Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Rusu I; Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Bain J; Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Rao AA; CoLabs, University of California, San Francisco, San Francisco, California, USA.
  • Andersen C; CoLabs, University of California, San Francisco, San Francisco, California, USA.
  • Law K; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Yang H; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Tsui J; CoLabs, University of California, San Francisco, San Francisco, California, USA.
  • Shen A; CoLabs, University of California, San Francisco, San Francisco, California, USA.
  • Davidson B; CoLabs, University of California, San Francisco, San Francisco, California, USA.
  • Kushnoor D; CoLabs, University of California, San Francisco, San Francisco, California, USA.
  • Shi Y; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Fan F; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Cheung A; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Zhang L; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Fong L; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Combes AJ; Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Pisco AO; CoLabs, University of California, San Francisco, San Francisco, California, USA.
  • Kattah MG; Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
  • Oh DY; ImmunoX Initiative, University of California, San Francisco, San Francisco, California, USA.
J Immunother Cancer ; 12(4)2024 Apr 19.
Article en En | MEDLINE | ID: mdl-38642938
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 cells were enriched in steroid-experienced and a validation data set of steroid-naïve CPI colitis, underscoring their pathogenic potential across steroid exposure. Distinct from ulcerative colitis, CPI colitis exhibited perturbed stromal metabolism (NAD+, tryptophan) impacting epithelial survival and inflammation. Endothelial cells in CPI colitis after anti-TNF and anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) upregulated the integrin α4ß7 ligand molecular vascular addressin cell adhesion molecule 1 (MAdCAM-1), which may preferentially respond to vedolizumab (anti-α4ß7).

CONCLUSIONS:

These findings nominate CD4+ RM and MAdCAM-1+ endothelial cells for targeting in specific subsets of CPI colitis patients.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Colitis / Linfocitos T CD8-positivos Límite: Humans Idioma: En Revista: J Immunother Cancer Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Colitis / Linfocitos T CD8-positivos Límite: Humans Idioma: En Revista: J Immunother Cancer Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos