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

Abstract

Context 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. Objective and methods 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. Result 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. Conclusion These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.

Gut microbiota in brain tumors: An emerging crucial player

“…The authors postulated that the imbalanced Firmicutes/Bacteroidetes ratio may induce inflammation and deficiency of beneficial metabolites, such as butyrate. However, later research conducted in a different ethnicity found different species that were increased ( Enterococcus , Prevotella , and Bifidobacterium ) and decreased ( Faecalibacterium and Megamonas ) 100 . Due to the limitations of 16 S rRNA amplicon sequencing, our group further utilized the metagenomic sequencing in GHPA patients and observed increased abundance of Oscillibacter and Enterobacter , along with decreased abundance of Blautia and Romboutsia 101 .…”

“…They found that fecal microbiota transplantation (FMT) from GHPA donors in tumor‐bearing nude mice increased tumor weight and volume, expanded PD‐L1 positive cell populations and CD8+ cell infiltration in tumor tissues, and increased levels of CD3 + CD8+ cell and sPD‐L1 in the peripheral circulation. This indicates that GHPA‐specific flora influences the status of the immune system, which may facilitate the escape of tumor cells from immune surveillance 100 …”

“…However, later research conducted in a different ethnicity found different species that were increased (Enterococcus, Prevotella, and Bifidobacterium) and decreased (Faecalibacterium and Megamonas). 100 Due to the limitations of 16 S rRNA amplicon sequencing, our group further utilized the metagenomic sequencing in GHPA patients and observed increased abundance of Oscillibacter and Enterobacter, along with decreased abundance of Blautia and Romboutsia. 101 We further observed a positive correlation between Enterobacter and GH/IGF-1 axis, implying the probable involvement of microbial variation in the pathophysi- Regarding abnormal microbial metabolites-mediated modulation, our group observed enhanced expression of genes related to amino acid metabolism and decreased abundance of genes in carbohydrate metabolism.…”

Identification of Malassezia globosa as a Gastric Fungus Associated with PD-L1 Expression and Overall Survival of Patients with Gastric Cancer

“…Gut microbiomes promote the polarization of M1/M2 macrophages, differentiation of Th1 lymphocytes, activation of cytotoxic T-cells, and upregulation of the expression of PD-L1 cointeractional molecule [6][7][8]. Intestinal microbiomes from the growth hormone-secreting pituitary adenoma (GHPA) patients promoted the mouse tumor growth, increased PD-L1 expression, and elevated the levels of PD-L1 in peripheral blood [9]. A great number of microbiotas including bacteria, fungi, and viruses colonize in the human stomach.…”

Growth hormone associated with treatment efficacy of immune checkpoint inhibitors in gastric cancer patients

“…As a growth factor with potential capacity to promote tumor cell mitosis and growth, GH could regulate the tumor microenvironment (TME), epithelial–mesenchymal transition (EMT), DNA damage repair, tumor vascular distribution, and chemotherapy resistance, thereby initiating the occurrence and development of tumors ( 14 – 16 ). Recent studies also showed that GH could mediate the expression of PD-1/PD-L1 and regulate CD4 + and CD8 + T lymphocytes, which might modify the immunotherapy efficacy of tumors by mediating the PD-1/PD-L1 pathway and/or TME ( 17 – 19 ). In the present study, the predictive value of GH for ICI efficacy in AGC patients is innovatively evaluated.…”