The role of T cell trafficking in CTLA-4 blockade-induced gut immunopathology

Immune checkpoint inhibitor (ICPI) can augment the anti-tumour response by blocking negative immunoregulators with monoclonal antibodies. The anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody is the first ICPI which has shown remarkable benefits in the clinical treatment of cancers....

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Bibliographic Details
Published in:BMC biology 2020-03, Vol.18 (1), p.29-29, Article 29
Main Authors: Zhang, Shashuang, Liang, Wenhua, Luo, Lingjie, Sun, Shan, Wang, Feng
Format: Article
Language:English
Subjects:
Analysis
Antigen receptors, T cell
Cancer therapies
Care and treatment
CD4 lymphocytes
CD4 T cells
Cell adhesion & migration
Clinical trials
Colitis
Control
CTLA-4 blockade
CTLA-4 protein
FDA approval
Gene expression
Immunoglobulins
Immunopathology
Immunotherapy
Inflammation
Inflammatory bowel disease
Lymphocytes
Lymphocytes T
Melanoma
Receptors
Rodents
T cells
Trafficking-blocking antibody
Tumors
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Summary:Immune checkpoint inhibitor (ICPI) can augment the anti-tumour response by blocking negative immunoregulators with monoclonal antibodies. The anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody is the first ICPI which has shown remarkable benefits in the clinical treatment of cancers. However, the increased activity of the immune system also causes some side effects called immune-related adverse events (irAEs). Colitis is one of the most common irAEs related to anti-CTLA-4 immunotherapy. We identified that CD4 T cells were the primary responders in CTLA-4 blockade and that the expansion of gut-homing CD4 T cells by anti-CTLA-4 therapy was independent of CD103. We used dextran sulfate sodium (DSS)-induced colitis mice as our model and tested the possibility of using a trafficking-blocking antibody to treat anti-CTLA-4 antibody-induced irAEs. We found that blocking T cell homing increased colitis severity in the context of CTLA-4 blockade and that gut-trafficking blockade had different effects on different Th subsets and could facilitate the proliferation of Th17 cells in the lamina propria (LP). Our data reveals the fundamental mechanism underlying trafficking-blocking antibody therapy for CTLA-4 blockade-induced colitis and provide a caution in regard to apply trafficking-blocking antibody treatment under CTLA-4 blockade condition.
ISSN:1741-7007
1741-7007
DOI:10.1186/s12915-020-00765-9