Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment.
Cell Mol Immunol
; 21(1): 47-59, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-38049523
ABSTRACT
A highly immunosuppressive tumor microenvironment (TME) and the presence of the bloodâbrain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma (HGG). Here, we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(IC) to establish a robust antitumor immune response in this registered clinical trial (NCT03392545). During the follow-up, 12/27 (44.4%) patients who achieved tumor control concomitant with survival benefit were regarded as responders in our study. We found that the T-cell receptor (TCR) repertoire in the TME was reshaped after poly(IC) treatment. Based on the RNA-seq analysis of tumor samples, the expression of annexin A1 (ANXA1) was significantly upregulated in the tumor cells of nonresponders, which was further validated at the protein level. In vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1 (FPR1) to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(IC). The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven TME. Moreover, ANXA1 could serve as a reliable predictor of response to poly(IC), with a notable predictive accuracy rate of 92.3%. In light of these notable findings, this study unveils a new perspective of immunotherapy for gliomas.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anexina A1
/
Glioma
Limite:
Humans
Idioma:
En
Revista:
Cell Mol Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China