Peripheral immune signatures associated with invasive behavior in pituitary neuroendocrine tumor: a blood-based analysis

BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) derived from adenohypophyseal cells are the third most frequent primary intracranial tumor. PitNETs that invades surrounding anatomical structures such as the cavernous sinus are defined as invasive PitNETs. Patients with invasive PitNETs often have co-morbidities and high recurrence rates. This study aimed to identify the cytokines associated with the invasive behavior of PitNETs and characterize the cytokine network and circulating immune cells in the peripheral immune microenvironment of invasive PitNETs. METHODS: Peripheral blood samples were collected from 87 patients with PitNET before transsphenoidal surgery for the resection of PitNET. Knosp grade 3 A to 4 tumors on magnetic resonance imaging (MRI) were defined as invasive PitNETs. After strict screening according to the exclusion criteria, 40 patients with invasive PitNET and 41 with noninvasive PitNET were enrolled in this study. Blood samples from 20 patients with invasive PitNET and 21 patients with non-invasive PitNET were randomly selected for multiplex plasma cytokine analysis. In addition, 20 peripheral blood samples were collected from healthy volunteers as controls. Blood samples from the remaining 20 patients with invasive PitNET and 20 patients with non-invasive PitNET were used for peripheral blood cell subpopulation analysis. RESULTS: memory T cells, Tregs, and macrophages, and lower levels of natural killer (NK) cells in the peripheral blood. CONCLUSION: MIF, MIP-1β, RANTES, IL-9, and TNF-β may serve as potential biomarkers for the diagnosis of invasive PitNET. The association between circulating immune cells and the cytokine network in the peripheral immune microenvironment is associated with the invasive behavior of PitNET.