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Invasive nonfunctioning pituitary adenomas (NFPAs) grow rapidly and the mechanisms are unclear. Among many complex mechanisms, the role of immunity in the development of NFPAs has not been fully explored. Here, we analyzed the clinical features 146 NFPA patients who underwent trans-sphenoidal surgery or craniotomy and examined the effects of immune tolerance in invasiveness of NFPA patients using fluorescence-activated cell sorting and immunohistochemical methods. We found patients with invasive NFPAs had more visual deficits and defective fields, higher tumor size, and lower white blood cell count compared with patients with noninvasive NFPAs. Additionally, compared with patients with noninvasive NFPAs, patients with invasive NFPAs had conspicuously lower CD3 − CD56 +  natural killer (NK) cells and significantly higher levels of CD3 + CD8 + CD28-T cells (CD8 +  Tregs) and interleukin-10 (IL-10) in peripheral blood. Moreover, patients with invasive NFPAs had lower infiltrated CD56 +  cells, less infiltrated CD28 +  cells, and significantly greater IL-10 expression. These results demonstrated that low CD56 +  cells infiltration and CD28 +  cells infiltration, as well as high IL-10 expression in pituitary tumor tissues, were related with increased invasiveness of NFPAs. Levels of CD3 − CD56 +  NK cells, CD8 +  Tregs and IL-10 in the peripheral blood could be feasible diagnostic markers for invasive NFPAs.

Alterations in CD8+ Tregs, CD56+ Natural Killer Cells and IL-10 Are Associated With Invasiveness of Nonfunctioning Pituitary Adenomas (NFPAs)