Loss of Trefoil Factor 1 Accelerates the Immune Response to Colorectal Cancer.
Animals
Colorectal Neoplasms
/ immunology
Trefoil Factor-1
/ genetics
Mice
Tumor Microenvironment
/ immunology
Mice, Knockout
Humans
Dendritic Cells
/ immunology
Cell Line, Tumor
B7-H1 Antigen
/ genetics
Immune Checkpoint Inhibitors
/ pharmacology
Mice, Inbred C57BL
CD8-Positive T-Lymphocytes
/ immunology
Colon cancer
PD-L1
Trefoil Factor Family 1
dendritic cells
immunotherapy
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Sep 2024
Sep 2024
Historique:
received:
05
07
2024
revised:
22
07
2024
accepted:
23
07
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
Recent studies suggest that PD-L1 expression in immune cells, rather than tumor cells, plays a key role in tumor immunity. Trefoil factor family 1 (TFF1) is a secreted protein expressed mainly by the gastrointestinal epithelium and is related to the development of malignant disease. This study investigated the effects of TFF1 on tumor immunity in a xenograft mouse model of colorectal cancer (CRC). MC38 cells were implanted in wild-type (WT) and TFF1KO mice, and the tumor micro-environment was investigated using immunohistochemistry. The circulating immune cells were analyzed using flow cytometry. Tumor growth was suppressed in TFF1KO mice. In the tumor microenvironment, CD8- and CD4-positive T cells and CD11c-positive dendritic cells (DCs) were frequently found in TFF1KO mice. When an immune checkpoint inhibitor was administered to these mice, almost half of the tumors in TFF1KO mice showed a complete response. The number of circulating PD-L1/DCs was markedly associated with tumor volume, with TFF1 deletion accelerating this effect and its injection decreasing it. These findings indicate that loss of TFF1 activates tumor immunity via frequent T-cell priming by DCs, and eventually suppresses tumor growth in CRC. In addition, the number of circulating PD-L1/DCs was identified as a predictive marker of checkpoint-inhibiting therapy efficacy. Loss of TFF1 resulted in accelerated immune response to colorectal cancer. Further studies are needed to investigate the precise mechanisms of TFF1 in immunotolerance and develop a novel TFF1-inhibiting immunotherapeutic strategy for CRC.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Recent studies suggest that PD-L1 expression in immune cells, rather than tumor cells, plays a key role in tumor immunity. Trefoil factor family 1 (TFF1) is a secreted protein expressed mainly by the gastrointestinal epithelium and is related to the development of malignant disease. This study investigated the effects of TFF1 on tumor immunity in a xenograft mouse model of colorectal cancer (CRC).
MATERIALS AND METHODS
METHODS
MC38 cells were implanted in wild-type (WT) and TFF1KO mice, and the tumor micro-environment was investigated using immunohistochemistry. The circulating immune cells were analyzed using flow cytometry.
RESULTS
RESULTS
Tumor growth was suppressed in TFF1KO mice. In the tumor microenvironment, CD8- and CD4-positive T cells and CD11c-positive dendritic cells (DCs) were frequently found in TFF1KO mice. When an immune checkpoint inhibitor was administered to these mice, almost half of the tumors in TFF1KO mice showed a complete response. The number of circulating PD-L1/DCs was markedly associated with tumor volume, with TFF1 deletion accelerating this effect and its injection decreasing it. These findings indicate that loss of TFF1 activates tumor immunity via frequent T-cell priming by DCs, and eventually suppresses tumor growth in CRC. In addition, the number of circulating PD-L1/DCs was identified as a predictive marker of checkpoint-inhibiting therapy efficacy.
CONCLUSION
CONCLUSIONS
Loss of TFF1 resulted in accelerated immune response to colorectal cancer. Further studies are needed to investigate the precise mechanisms of TFF1 in immunotolerance and develop a novel TFF1-inhibiting immunotherapeutic strategy for CRC.
Identifiants
pubmed: 39197918
pii: 44/9/3757
doi: 10.21873/anticanres.17200
doi:
Substances chimiques
Trefoil Factor-1
0
Tff1 protein, mouse
0
B7-H1 Antigen
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3757-3769Informations de copyright
Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.