Hyperthermia inhibits the progression of gastric cancer by downregulating PLEK2/PD-L1 and possibly participates in immunomodulation

Abstract

Background: Hyperthermia is used as an adjunctive treatment for gastric cancer; however, the corresponding antitumor mechanism remains unclear.

Objective: To investigate the expression of PLEK2 in gastric cancer and the mechanism by which hyperthermia inhibits gastric cancer progression and participating in immunomodulation.

Methods: PLEK2 was screened by combining microarray analysis with gene knockdown and proliferation assays. Analysis based on the TCGA database, GEPIA website, and detection of clinical samples was employed to investigate the expression and correlation of PLEK2 and PD-L1. Knockdown of the expression PLEK2, subsequent experiments including western blotting, RT-qPCR, cell functional assays, and flow cytometry were used to assess the effects on cell migration, invasion, viability, and apoptosis. Intervention with hyperthermia to explore its effects. To evaluate the impact on immunity by detecting T cell proliferation and the release of IFNγ, activated T cells were co-cultured with the target cells.

Results: Hyperthermia significantly reduced the expression of PLEK2 and PD-L1, while both were increased in gastric cancer. Knockdown of PLEK2 inhibited PD-L1 expression and significantly inhibited the proliferation, invasion, migration, and viability of gastric cancer cells. A decrease in PLEK2 expression promotes cell apoptosis. Although it cannot affect the proliferation of activated T cells, it can partially reverse IFNγ suppression.

Conclusion: PLEK2 plays a promoting role in gastric cancer, and hyperthermia downregulates PLEK2/PD-L1, which further inhibits cell proliferation, invasion, and migration, promotes cell apoptosis, and possibly participates in immune regulation.

Keywords: Gastric cancer; Hyperthermia; Immunomodulation; Invasion and migration; PD-L1; PLEK2.