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Generation of Tumor Organoids from Genetically Engineered Mouse Models of Prostate Cancer
Published on: June 13, 2019
TBX21 correlates with an immunosuppressive tumor microenvironment and Treg/Th17 imbalance in prostate cancer
Heng Wang1, Zhaofei Liu1, Xiangjun Xu2
1Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Background:
Prostate cancer (PCa) remains a major health burden, and identifying target molecules will provide new research ideas for treating PCa. TBX21 is a transcriptional factor with critical functions in tumor development, roles of which in PCa were studied herein.
Methods:
TBX21 expression was evaluated by RNA-seq, RT-PCR, Western blot, and immunohistochemistry in PCa tissues and cell lines. Functional assays were performed using LNCaP and 22RV1 cells with TBX21 knockdown to assess proliferation and apoptosis. Tumor growth and immune alterations were examined in xenograft and humanized immune cell models, while flow cytometry and Western blot were used to characterize immune cell subsets and effector molecules.
Results:
TBX21 expression was significantly elevated in PCa tissues and cell lines. TBX21 knockdown was associated with reduced proliferation and increased apoptosis in vitro and suppressed tumor growth in vivo. In humanized xenografts, TBX21 silencing was accompanied by a decrease in regulatory T cells (Treg) and an increase in Th17 and cytotoxic CD8+ T cells, together with enhanced expression of effector molecules (TNF-α, GZMB). Co-culture experiments showed that TBX21-deficient tumor cells reduced the induction of CD25+Foxp3+ Treg cells from activated CD4+ T cells.
Conclusion:
TBX21 is associated with tumor progression and an immunosuppressive microenvironment in PCa, underscoring its potential role in modulating the tumor-immune balance.
Insights
TBX21 is elevated in prostate cancer (PCa) and promotes tumor growth. Silencing TBX21 reduces PCa progression and reshapes the tumor immune microenvironment, offering therapeutic potential.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Prostate cancer (PCa) presents a significant health challenge, necessitating novel therapeutic targets.
- The transcription factor TBX21 plays a role in tumor development, and its specific involvement in PCa warrants investigation.
Purpose of the Study:
- To investigate the role of TBX21 in prostate cancer progression.
- To explore the impact of TBX21 on the tumor immune microenvironment in PCa.
Main Methods:
- TBX21 expression was analyzed using RNA-seq, RT-PCR, Western blot, and immunohistochemistry in PCa tissues and cell lines.
- Functional assays, including cell proliferation and apoptosis studies, were conducted with TBX21 knockdown in PCa cell lines.
- Tumor growth, immune cell infiltration, and effector molecule expression were assessed in xenograft and humanized immune cell models.
Main Results:
- TBX21 expression is significantly upregulated in PCa tissues and cell lines.
- TBX21 knockdown inhibited PCa cell proliferation and induced apoptosis in vitro, and suppressed tumor growth in vivo.
- TBX21 silencing modulated the immune microenvironment, decreasing regulatory T cells (Treg) and increasing Th17 and cytotoxic CD8+ T cells, with enhanced effector molecule production.
Conclusions:
- TBX21 is implicated in prostate cancer progression and the establishment of an immunosuppressive tumor microenvironment.
- Targeting TBX21 may represent a viable strategy for modulating the tumor-immune balance in PCa.
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