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Updated: Jul 16, 2026
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Single-cell analysis reveals that TCF7L2 facilitates the progression of ccRCC via tumor-associated macrophages
Fengran Guo1, Yilong Gao2, Pengfei Zhou3
1Department of Urology, Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Background:
Tumor-associated macrophages (TAMs) play an important role in the recurrence and progression of clear cell renal cell carcinoma (ccRCC). However, the specified mechanism has not been elucidated.
Methods:
Single-cell and transcriptome analysis were applied to characterize the heterogeneity of TAMs. SCENIC would infer regulators of different subsets of TAMs. The CellChat algorithm was used to infer macrophage-tumor interaction networks, whereas pseudo-time traces were used to parse cell evolution and dynamics.
Results:
In this study, single-cell transcriptomic data of ccRCC were analyzed. Notably, the macrophages were clustered to select the cluster with a tendency toward M2-type TAM, which has an impact on the occurrence and metastasis of ccRCC. This macrophage cluster was defined as "TAM2". And this study revealed that TCF7L2 as a potential transcription factor regulating TAM2 transcriptional heterogeneity and differentiation. Pseudotime traces showed TCF7L2 trajectories during TAM2 cell cluster development. In addition, the results of cell interaction showed that TAM2 had the highest number and strength of interactions with cancer cells and endothelial cells. In vitro experiments, this study found that TCF7L2 was highly expressed in TAMs and promoted the polarization of macrophages to M2-type macrophages. And then overexpression of TCF7L2 in macrophages markedly promoted ccRCC invasion and proliferation.
Conclusion:
TCF7L2 could play a key role in the progression of ccRCC via enhancing TAMs recruitment and M2-type polarization.
Insights
Tumor-associated macrophages (TAMs) drive clear cell renal cell carcinoma (ccRCC) progression. This study identifies TCF7L2 as a key factor promoting TAM recruitment and M2 polarization, thus enhancing ccRCC invasion and metastasis.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Tumor-associated macrophages (TAMs) are implicated in clear cell renal cell carcinoma (ccRCC) recurrence and progression.
- The precise mechanisms underlying TAM involvement in ccRCC remain unclear.
Purpose of the Study:
- To elucidate the role and regulatory mechanisms of TAMs in ccRCC progression.
- To identify key molecular players involved in TAM heterogeneity and function within the ccRCC microenvironment.
Main Methods:
- Single-cell and transcriptome analysis to characterize TAM heterogeneity.
- SCENIC for inferring regulatory networks.
- CellChat for analyzing cell-cell interactions.
- Pseudotime analysis for cell dynamics.
- In vitro experiments to validate findings.
Main Results:
- Identified a specific TAM subset, "TAM2," associated with ccRCC occurrence and metastasis.
- TCF7L2 identified as a crucial transcription factor regulating TAM2 differentiation and heterogeneity.
- TAM2 exhibits significant interactions with cancer and endothelial cells.
- TCF7L2 overexpression in macrophages promotes ccRCC invasion and proliferation in vitro.
Conclusions:
- TCF7L2 plays a pivotal role in ccRCC progression.
- TCF7L2 enhances ccRCC by promoting TAM recruitment and M2-type polarization.
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