Downregulation of S100A11 promotes T cell infiltration by regulating cancer-associated fibroblasts in prostate cancer.
Int Immunopharmacol
; 128: 111323, 2024 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-38286714
ABSTRACT
OBJECTIVE:
This study aims at revealing the relationship between S100A11 and cancer-associated fibroblasts (CAFs) in prostate cancer and improving T cell infiltration into solid tumors.METHODS:
H&E, IHC and Sirius red staining were used to detect the stroma content in prostate cancer tissues. Stable S100A11 knockdown cell lines DU 145, 22Rv1, RM-1 and NOR-10 were established by lentivirus transfection. Co-culture system of RM-1 and CAFs was established. CCK-8, wound healing and transwell were proceeded to determine proliferation, migration and invasion of prostate cancer cells. Stably knocked-down RM-1 and CAFs were co-injected into C57BL/6 mice to detect the role of S100A11 in vivo. CAFs, CD4+ T cell and CD8+ T cell in these tumors were assessed by IF. T cell profile was analyzed by flow cytometry.RESULTS:
A significant amount of stroma exists in prostate cancer tissues. Downregulation of S100A11 inhibits proliferation, migration and invasion of human prostate cancer cells in vitro, and suppresses the expression of cancer-associated fibroblasts (CAFs) in vivo. Knockdown of S100A11 enhances the inhibitory effect of Erdafitinib on CAFs in both the co-culture system and in vivo. The combined knockdown of S100A11 in tumor cells and CAFs shows a superior therapeutic effect compared to the individual knockdown in tumor cells alone. Knockdown of S100A11, both in RM-1 and CAFs, combined with Erdafitinib treatment reduces tumorigenicity by suppressing the content of CAFs and increasing the infiltration of CD4+ T cell and effective CD8+ T cell in tumor.CONCLUSION:
Downregulation of S100A11 plays a crucial role in enhancing the therapeutic response to Erdafitinib and reversing immunosuppressive tumor microenvironment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Cancer-Associated Fibroblasts
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Netherlands