Baicalin attenuates the immune escape of oral squamous cell carcinoma by reducing lactate accumulation in tumor microenvironment

Introduction: The acidic microenvironment caused by excessive lactate accumulation could inhibit immune lymphocytes antitumor activity and promote the immune escape of tumor cells. Baicalin is an active flavonoid isolated from Scutellaria baicalensis Georgi, a traditional Chinese medicinal herb with antioxidant and anti-inflammatory properties.

Objectives: The present study aims to investigate whether and how baicalin inhibits oral squamous cell carcinoma (OSCC) acidic microenvironment and attenuates immune escape.

Methods: Baicalin was dose-dependently administrated to OSCC cells (0-50 μmol/L). Co-culture system was constructed by OSCC cells and activated PBMCs. The proliferation and migration of OSCC cells were tested by CCK-8, colony formation, EdU, transwell assays. The cytokines were tested by ELISA kits. Mechanistical exploration was verified by RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and RNA stability assays.

Results: Results indicated that baicalin dose-dependently repressed the proliferation and migration of OSCC cells, and strengthened the antitumor immune activity of activated PBMCs to OSCC cells. Moreover, baicalin repressed the lactate accumulation, acidification and m⁶A modification level of OSCC cells. Molecular docking and MeRIP-Seq revealed that baicalin targeted LDHA via m⁶A-IGF2BP3-dependent manner to reduce lactate accumulation and PD-L1 expression in co-culture microenvironment.

Conclusion: This study revealed the anti-tumor activity of baicalin for OSCC by reducing lactate accumulation and attenuating the immune escape in tumor microenvironment, which provided a novel insight to improve our understanding in the treatment of traditional Chinese medicine on human cancer.