The accumulation of myeloid-derived suppressor cells participates in abdominal infection-induced tumor progression through the PD-L1/PD-1 axis.

Abstract

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide, with gastrectomy being the primary treatment option. Sepsis, a systemic inflammatory response to infection, may influence tumor growth by creating an immunosuppressive environment conducive to cancer cell proliferation and metastasis. Here, the effect of abdominal infection on tumor growth and metastasis was investigated through the implementation of a peritoneal metastasis model and a subcutaneous tumor model. In a murine model induced by cecal ligation and puncture (CLP) to simulate the effects of sepsis, we observed significant immune dysregulation, including T-cell exhaustion and the release of myeloid-derived suppressor cells (MDSCs). This immune alteration was associated with increased programmed cell death protein 1 (PD-1) expression on T cells and programmed cell death 1 ligand 1 (PD-L1) expression on MDSCs within the tumor microenvironment, fostering an immune-suppressive environment. Polymorphonuclear MDSCs (PMN-MDSCs) expressing elevated PD-L1 after sepsis demonstrated more substantial suppressive effects on T-cell proliferation than controls. Treatment with anti-PD-1 monoclonal antibodies successfully restored T-cell function, reduced mortality, and decreased metastasis in CLP mice. These findings emphasize the impact of sepsis on tumor progression and suggest targeting the PD-1/PD-L1 axis as a potential therapeutic strategy for managing immune dysfunction in patients with cancer.