Abstract
The tumor microenvironment (TME) includes resident and infiltrative non-tumor cells, as well as blood and lymph vessels, extracellular matrix molecules, and numerous soluble factors, such as cytokines and chemokines. While the TME is now considered to be a prognostic tool and a therapeutic target for many cancers, little is known about its composition in pituitary tumors. This review summarizes our current knowledge of the TME within pituitary tumors and the strong interest in TME as a therapeutic target. While we cover the importance of angiogenesis and immune infiltrating cells, we also address the role of the elusive folliculostellate cells, the emerging literature on pituitary tumor-associated fibroblasts, and the contribution of extracellular matrix components in these tumors. The cases of human pituitary tumors treated with TME-targeting therapies are reviewed and emerging concepts of vascular normalization and combined therapies are presented. Together, this snapshot overview of the current literature pinpoints not only the underestimated role of TME components in pituitary tumor biology, but also the major promise it may offer for both prognosis and targeted therapeutics.
Highlights
Pituitary tumors are common tumors of the anterior pituitary gland that can appear in up to a fifth of the general population [1,2]
The identification of factors leading to an aggressive phenotype and the discovery of new therapeutic targets/treatment options are of particular importance for the understanding of the biology of pituitary tumors and the management of aggressive pituitary tumors, including carcinomas
Vidal et al, who assessed microvessel densities by performing IHC for the CD34 antigen in a series of 157 pituitary adenomas (PAs) and 7 pituitary carcinomas, found the highest percentage of microvessel density was in pituitary carcinomas [14]. While these observations support the view that PAs are generally less vascularized than the normal pituitary gland and that pituitary carcinomas are more vascularized than PAs, the comparative analysis of tumor angiogenesis between different PA subtypes has yielded contradictory results, as different studies have reported divergent findings regarding which hormonal subtype PA appears to be more vascularized, and regarding the association between angiogenesis and clinical traits, such as invasiveness [12,13,14,15,16]
Summary
Pituitary tumors are common tumors of the anterior pituitary gland that can appear in up to a fifth of the general population [1,2]. Clinical management of aggressive pituitary tumors is difficult due to their resistance and/or multiple recurrences despite the correct use of surgery, conventional medical treatment, and radiotherapy [3]. The identification of factors leading to an aggressive phenotype and the discovery of new therapeutic targets/treatment options are of particular importance for the understanding of the biology of pituitary tumors and the management of aggressive pituitary tumors, including carcinomas. While the existence and importance of the TME as both a prognostic tool and a therapeutic target is well-accepted and has been described regarding numerous cancers [6,7], research on the pituitary tumor TME is still scarce. We provide an overview of the current known composition and function of the microenvironment of pituitary tumors and of its importance as a therapeutic target
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