Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway.

Background: The tumor immune microenvironment (TIME) and its impact on the prognoses and treatment of lung adenocarcinoma (LUAD) represent a major focus of research in this field. The present study primarily elucidates the role of RGS17 in TIME of LUAD.

Methods: A comprehensive array of analytical methods was employed to assess the gene expression levels, including RT-qPCR, Western blots assay and Immunohistochemistry. The assessment of cell apoptosis and viability was conducted through the utilization of Flow cytometry, Colony formation, or CCK-8 assays. To comprehensively evaluate glycolysis, the glucose consumption, lactate production and extracellular acidification rate (ECAR) were detected.

Results: RGS17 was highly expressed in LUAD patients, which predicted adverse prognosis of LUAD patients. Functionally, RGS17 promoted LUAD tumor growth by hindering the anti-tumor immune response. Specifically, knockdown of RGS17 in tumor cells was observed to result in increased CD8 + T cell infiltration into the tumors, thereby impeding LUAD tumor growth. Furthermore, tumor-secreted RGS17 impeded CD8 + T cell function by reducing IFN-γ and Granzyme B secretion, thus impeding the anti-tumor immune response. Mechanically, RGS17 impeded glycolysis in CD8 + T cells by regulating the PI3K/AKT pathway.

Conclusion: Tumor-secreted RGS17 impairs CD8 + T cell cytotoxicity in LUAD through impeding glycolysis mediated by PI3K/AKT pathway, thereby promoting tumor growth.