SOX17 expression in tumor-penetrating vessels in relation to CD8+ T-cell infiltration in cancer stroma niches.

Introduction: Sex-determining region Y-related high-mobility group box 17 protein (SOX17), a proangiogenic transcription factor, is specifically expressed in tumor endothelial cells (TECs) of implanted Lewis lung carcinoma. However, the expression profile of SOX17 is largely unknown in human lung cancer. We aimed to elucidate SOX17 expression in cancer cells and the tumor microenvironment of lung adenocarcinoma.

Methods: In the present study, we examined SOX17 expression in whole-tissue specimens of 83 lung adenocarcinomas by immunohistochemistry.

Results: SOX17 immunoreactivity was minimal in lung adenocarcinoma cells, except in five non-mucinous adenocarcinomas in situ. SOX17 was also expressed in cultured A549 lung adenocarcinoma cells, which is widely used as a model of malignant alveolar type II epithelial cells. Notably, SOX17 immunoreactivity was found in endothelial cells of tumor-penetrating vessels in 19 of 83 lung adenocarcinoma tissue specimens, with statistical significance to stromal infiltration of CD8⁺ T cells (p < 0.01) but was not associated with the number of tertiary lymph nodes. Although not statistically significant, SOX17 immunoreactivity was related to favorable patient outcomes.

Conclusion: Our findings indicate that SOX17 might play a pleiotropic role in lung adenocarcinoma in cancer cells and stromal niches. SOX17-mediated CD8⁺ T-cell-rich tumor microenvironment might attract interest in improving the effect of cancer immunotherapy.