Abstract

IntroductionSomatotroph pituitary tumours are often resistant to first-generation somatostatin analogues and can invade the surrounding structures, limiting the chances of curative surgery. Recent studies suggested that the immune microenvironment and pro-angiogenic factors can influence neuroendocrine tumour prognosis. In this study, we aimed to investigate the prognostic role of immune cell-specific markers and endocan, a proteoglycan involved in neoangiogenesis and cell adhesion, in a cohort of acromegaly patients who underwent pituitary surgery as first-line treatment.Subjects and methodsSixty four eligible subjects were identified. CD4+, CD8+ and CD68+ cells and endocan expression were evaluated by immunohistochemistry and results correlated with clinical and neuroradiological findings. Responsiveness to somatostatin analogues was assessed in patients with persistent disease following surgery.ResultsThe number of CD8+ lymphocytes was significantly lower in tumours with cavernous sinus invasion (median 0.2/HPF, IQR: 2.2) compared with those without cavernous sinus invasion (median 2.4/HPF, IQR: 2.3; P = 0.04). Tumours resistant to first-generation somatostatin analogues had lower CD8+ lymphocytes (median 1/HPF, IQR: 2.4) compared with responders (median 2.4/HPF, IQR: 2.9; P = 0.005). CD4+ lymphocytes were observed sporadically. The number of CD68+ macrophages and the endothelial or tumour cell endocan expression did not differ based on tumour size, cavernous sinus invasion or treatment responsiveness.ConclusionsOur study suggests that a lower number of CD8+ lymphocytes is associated with cavernous sinus invasion and resistance to treatment with first-generation somatostatin analogues in acromegaly patients. These results highlight a potential role of the tumour immune microenvironment in determining the prognosis of somatotroph pituitary tumours.

Highlights

  • Somatotroph pituitary tumours are often resistant to first-generation somatostatin analogues and can invade the surrounding structures, limiting the chances of curative surgery

  • Macrophages can be differentiated into M1 and M2 macrophages, with Tumour-associated macrophages (TAMs) generally thought to resemble M2-polarised macrophages, which play a role in promoting tumour cell proliferation and progression as well as inhibiting immune response mediated by T lymphocytes [19]

  • Out of the 64 enroled patients, 40 patients were affected by persistent acromegaly after surgery and, 21 patients were treated with octreotide LAR and 19 patients with lanreotide ATG

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Summary

Introduction

Somatotroph pituitary tumours are often resistant to first-generation somatostatin analogues and can invade the surrounding structures, limiting the chances of curative surgery. Somatotroph pituitary neuroendocrine tumours (PitNETs) [1] are, in most cases, benign, they can be locally invasive, limiting the chances of radical surgical resection, Dermopatico dell’Immacolata, IDI-IRCCS, Rome, Italy 5 Institute of Neurosurgery, Fondazione Policlinico Universitario A. Recent studies suggested that neoangiogenesis and the tumour immune microenvironment play a role in determining the prognosis of neuroendocrine tumours [9,10,11,12,13,14,15]. Macrophages can be differentiated into M1 and M2 macrophages, with TAMs generally thought to resemble M2-polarised macrophages, which play a role in promoting tumour cell proliferation and progression as well as inhibiting immune response mediated by T lymphocytes [19]. Despite extensive studies on the tumour immune microenvironment in many solid malignancies, little data are available on PitNETs and other neuroendocrine tumours

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