Unveiling the immunosuppressive role of splenectomy-induced miRNA hsa-7b-5p in promoting pancreatic cancer growth and metastasis

Abstract

Abstract The spleen is a vital organ in the immune system, but due to the anatomical location of the pancreas, splenectomy is often performed in conjunction with distal pancreatectomy. However, controversy remains regarding the increased risk of recurrence and metastasis after surgery. Previous studies have shown that splenectomy promotes the growth and spread of pancreatic cancer in mice by reducing the ratio of CD4 to Foxp3 and CD8 to Foxp3. Nevertheless, it remains unclear whether spleen deficiency affects other immune cells. Clinical observations have shown that splenectomy leads to an immunosuppressive status and increases the risk of recurrence and metastasis in some pancreatic cancer patients. Here, we established an orthotopic pancreatic cancer model with splenectomy and found that the tumor burden increased significantly. Flow cytometry analysis demonstrated that the percentage of MDSCs and CD8 + PD1 + T cells in tumors and peripheral blood significantly increased, while the infiltration of CD4 + T cells, CD8 + T cells, and natural killer cells decreased. Bulk sequencing analysis revealed that the expression of miRNA hsa-7b-5p increased in tumor tissues after splenectomy, which was associated with pancreatic cancer staging and immunosuppressive status. Similar results were obtained in vivo by constructing a KPC-miRNA hsa-7b-5p-sh cell line. These findings suggest that splenectomy enhances the expression of miRNA hsa-7b-5p, inhibits the tumor immune microenvironment, and promotes pancreatic cancer growth.