The intestinal flora of patients with GHPA affects the growth and the expression of PD-L1 of tumor

Abstract

Pituitary adenoma (PA) is a common intracranial tumor. The evidence indicates that the tumor immune microenvironment (TIME) is associated with PA and that the intestinal flora influences other tumors growth through interacting with the TIME. However, how the intestinal microbial flora contributes to the development of PA through the immune response is unknown. Here we used high-throughput Illumina MiSeq sequencing targeting the V3−V4 region of the 16S ribosomal RNA gene to investigate the intestinal flora of patients with growth hormone-secreting pituitary adenoma (GHPA), nonfunctional pituitary adenoma (NFPA), and healthy controls. We determined their effects on tumor growth and the TIME. Fecal microbiota transplantation (FMT) was performed after adoptive transfer via peripheral blood mononuclear cells to tumor-bearing nude mice, which allowed the study of the immune response. We discovered differences in the structures and quantities of intestinal flora between patients with GHPA, patients with NFPA, and healthy controls. After FMT, the intestinal flora of GHPA patients promoted the growth of tumors in mouse models. The number of programmed cell death ligand 1 (PD-L1)-positive cells increased in tumor tissues as well as the extent of infiltration of CD8+ cells. Increased numbers of CD3+CD8+ cells and increased levels of sPD-L1 were detected in peripheral blood. These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.