Dr Wang on Key Findings From a Study of the Tumor Microenvironment in ccRCC

“Moving forward, we propose not only targeting the exhausted immune cells at the tumor site but also targeting the stroma and fibroblast physical barrier to increase the penetration of tumor-infiltrating leukocytes into the cancer niches.”

Yufei Wang, PhD, instructor in medicine, immunology and virology, Dana-Farber Cancer Institute, discussed data from a preclinical study that examined how the metastasis of clear cell renal cell carcinoma (ccRCC) could rewire the tumor microenvironment and lead to increased immunosuppression and fibrosis.

During the 2025 AACR Annual Meeting, Wang presented data from the study in a poster which demonstrated that the spatial architecture of the tumor microenvironment had an effect on primary and metastatic ccRCC cells. Wang and her coauthors also showed that there was a relationship between the spatial organization of the cellular context and cell to cell communication.

These findings suggest that immune cells and cancer-associated fibroblasts are essential comments of the tumor microenvironment of ccRCC. The results also indicated that the interaction of these components is a major factor in disease progression and response to therapy in patients with ccRCC.

In metastatic ccRCC cells, the tumor niche was surrounded by a fibroblast barrier that excluded tumor-infiltrating leukocytes from entering the tumor niche, Wang explained. Additionally, lung-metastatic ccRCC cells demonstrated a more immune-exclusive phenotype with greater immunosuppression compared with primary ccRCC cells, she continued.

To conduct their study, Wang and her coauthors profiled 3 primary and 3 lung-metastatic ccRCC samples using the CosMx platform, which employs a 999-gene transcriptome with spatial coordinates. Following cell segmentation and annotation, the study authors incorporated cellular contest and spatial data to identify tumor niches. Twelve distinct tumor niches formed by 25 cell types were identified, including stroma, alveolar, tertiary lymphoid structure, and mast niches. The niches were then analyzed via a spatial profiling platform to determine cellular composition.

In the future, Wang proposed targeting both the exhausted immune cells at the tumor site as well as at the stroma and fibroblast physical barrier. This approach could increase the penetration of tumor-infiltrating leukocytes into ccRCC cancer niches, she concluded.