Cutting Edge: Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice.
J Immunol
; 199(11): 3733-3737, 2017 12 01.
Article
in En
| MEDLINE
| ID: mdl-29061768
ABSTRACT
Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti-TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti-TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti-TIM-3-treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice. Anti-TIM-3 mAb was associated with increased numbers of myofibroblasts, collagen deposition, and TGF-ß1 production in lungs. TIM-3 expression was only detected on alveolar macrophages that protect against fibrosis by apoptotic cell clearance. Treatment with anti-TIM-3 mAb inhibited the phagocytic ability of alveolar macrophages in vivo, resulting in the defective clearance of apoptotic cells in lungs. In summary, anti-TIM-3 mAb treatment might cause pneumonitis and it should be used with caution in clinical settings.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pneumonia
/
Pulmonary Fibrosis
/
Macrophages, Alveolar
/
Hepatitis A Virus Cellular Receptor 2
/
Immunotherapy
/
Lung
/
Antibodies, Monoclonal
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
J Immunol
Year:
2017
Type:
Article
Affiliation country:
Japan