Emerging insights into the pathophysiology of pituitary tumour microenvironment

Pituitary tumours (PiTs) are a heterogeneous group of diseases of the anterior pituitary gland. While they are often described as rare diseases, the actual prevalence of these tumours is higher than commonly believed, accounting for at least 15% of all intracranial tumours. Yet, the high heterogeneity of the different PiTs (intra- and inter-patient heterogeneity), rooted in part in the intrinsic cellular diversity of the normal pituitary gland itself, has significantly limited the understanding of the biological mechanisms linked to their development, progression and aggressive behaviour. Like other cancer types, understanding the tumour microenvironment (TME) might help to better understand the pathophysiology of PiT-cells beyond genetics, epigenetics, transcriptomics and proteomics, and could constitute a personalized approach to dealing with these complex and heterogeneous endocrine-related tumours and to develop novel diagnostic, prognostic and future therapeutic tools. Importantly, the concept of TME relies on the notion that tumours are more than a group of tumour cells, rather being a heterogeneous mixture of tumour and non-tumour cells interacting with local components (growth factors, cytokines, etc.) within a remodelled tumour extracellular matrix (ECM). In this review, we will focus on describing the latest research on this complex TME-PiTs architecture network, which could bring a new era in diagnosing and treating these heterogeneous and complex endocrine-related cancers.