Cover Image

Distinct immune-effector and metabolic profile of CD8+ T cells in patients with autoimmune polyarthritis induced by therapy with immune checkpoint inhibitors

Objectives Rheumatic immune-related adverse events (irAE) such as (poly)arthritis in patients undergoing immune checkpoint inhibitor (ICI) treatment pose a major clinical challenge. ICI therapy improves CD8+ T cell (CD8) function, but CD8 contributes to chronic inflammation in autoimmune arthritis (...

Full description

Saved in:
Bibliographic Details
Main Authors: Gente, Karolina (Author) , Kraus, Franziska V. (Author) , Carvalho, Rui A. (Author) , Lorenz, Holger (Author) , Hoerth, Christian (Author) , Günther, Janine (Author) , Klika, Karel D. (Author) , Graf, Jürgen (Author) , Diekmann, Leonore (Author) , Schank, Timo Emanuel (Author) , Christopoulos, Petros (Author) , Hassel, Jessica C. (Author) , Lorenz, Hanns-Martin (Author) , Souto-Carneiro, Maria Margarida (Author)
Format: Article (Journal)
Language:English
Published: 3 August 2022
In: Annals of the rheumatic diseases
Year: 2022, Volume: 81, Issue: 12, Pages: 1730-1741
ISSN:1468-2060
DOI:10.1136/ard-2022-222451
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1136/ard-2022-222451
Verlag, kostenfrei, Volltext: https://ard.bmj.com/content/81/12/1730
Get full text
Author Notes:Karolina Benesova, Franziska Viktoria Kraus, Rui A. Carvalho, Holger Lorenz, Christian H. Hörth, Janine Günther, Karel D. Klika, Jürgen Graf, Leonore Diekmann, Timo Schank, Petros Christopoulos, Jessica C. Hassel, Hanns-Martin Lorenz, Margarida Souto-Carneiro
Description
Summary:Objectives Rheumatic immune-related adverse events (irAE) such as (poly)arthritis in patients undergoing immune checkpoint inhibitor (ICI) treatment pose a major clinical challenge. ICI therapy improves CD8+ T cell (CD8) function, but CD8 contributes to chronic inflammation in autoimmune arthritis (AA). Thus, we investigated whether immune functional and metabolic changes in CD8 explain the development of musculoskeletal irAE in ICI-treated patients. - Methods Peripheral CD8 obtained from ICI-treated patients with and without arthritis irAEs and from AA patients with and without a history of malignancy were stimulated in media containing 13C-labelled glucose with and without tofacitinib or infliximab. Changes in metabolism, immune-mediator release, expression of effector cell-surface molecules and inhibition of tumour cell growth were quantified. - Results CD8 from patients with irAE showed significantly lower frequency and expression of cell-surface molecule characteristic for activation, effector-functions, homing, exhaustion and apoptosis and reduced release of cytotoxic and proinflammatory immune mediators compared with CD8 from ICI patients who did not develop irAE. This was accompanied by a higher glycolytic rate and ATP production. Gene-expression analysis of pre-ICI-treated CD8 revealed several differentially expressed transcripts in patients who later developed arthritis irAEs. In vitro tofacitinib or infliximab treatment did not significantly change the immune-metabolic profile nor the capacity to release cytolytic mediators that inhibit the growth of the human lung cancer cell line H838. - Conclusions Our study shows that CD8 from ICI-treated patients who develop a musculoskeletal irAE has a distinct immune-effector and metabolic profile from those that remain irAE free. This specific irAE profile overlaps with the one observed in CD8 from AA patients and may prove useful for novel therapeutic strategies to manage ICI-induced irAEs.
Item Description:Gesehen am 12.06.2023
Physical Description:Online Resource
ISSN:1468-2060
DOI:10.1136/ard-2022-222451

Similar Items