Tumour-infiltrating cytotoxic T lymphocytes in somatotroph pituitary neuroendocrine tumours

Abstract

Introduction Somatotroph 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 methods Sixty 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. Results The 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. Conclusions Our 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.

The Immune Profile of Pituitary Adenomas and a Novel Immune Classification for Predicting Immunotherapy Responsiveness

“…Instead, we found that the tumor size and patient age presented different correlations with the distribution of TIICs, mostly neutrophils and T cells. Some of these results are novel to those of previous studies ( 13 , 18 , 19 , 58 ).…”

“…An improved understanding of the immune characteristics of the TME and novel classifications based on different immune features might provide insights into the mechanisms of different immunotherapy responses and serve as resources for future targeted studies ( 16 , 17 ). Several studies have investigated intratumoral T-cell infiltration and programmed death-ligand 1 (PD-L1) expression in PAs ( 13 , 18 , 19 ). Iacovazzo et al ( 19 ) demonstrated that a lower number of CD8 + T cells is related to both the invasion of PAs to the cavernous sinus and resistance to treatment.…”

“…Several studies have investigated intratumoral T-cell infiltration and programmed death-ligand 1 (PD-L1) expression in PAs ( 13 , 18 , 19 ). Iacovazzo et al ( 19 ) demonstrated that a lower number of CD8 + T cells is related to both the invasion of PAs to the cavernous sinus and resistance to treatment. Studies conducted by Mei et al ( 18 ) and Wang et al ( 13 ) concluded that PD-L1 expression is higher in functioning PAs and correlated with tumor aggressiveness.…”

Endocan, VEGF, FGF2 and PDGF Expression in Pituitary Tumors. A Precise Angiogenic Marker Relationship in the Context of Tumor Invasiveness

“…Instead, in another study only endothelial endocan expression correlated with tumor size and recurrence, both signs of aggressiveness, and no correlation with invasion was found (17). Similarly, no relation of endocan and cavernous sinus invasion or resistance to treatment with rst-generation somatostatin analogues was found in acromegaly patients (39), though endocan may participate in the resistance of prolactinomas to dopamine therapy (34).…”

Research advances on the immune research and prospect of immunotherapy in pituitary adenomas

“…In the PA stroma, CD68+ macrophages > CD4+ T cells and CD8+ T cells. [ 31 , 41 , 47 , 48 , 51 – 53 ] 35; 134; 28;35; 64; 115; 15 Immunohistochemistry; Computational approach; flow cytometry 2021; 2020; 2020; 2015; 2020; 2020; 2019 CD147 Invasion tumors > non-invasive tumors. [ 55 ] 55 Immunohistochemistry 2005 CD163 The most abundant type of immune cell in PitNETs, and mainly CD163 +.…”