Pituitary adenomas (PAs) are neoplasms derived from the endocrine cells of the anterior pituitary gland. Most frequently, they are benign tumors, but may sometimes display an aggressive course, and in some cases metastasize. Their biology, including their wide range of behavior, is only partly understood. In terms of therapeutic targeting, most PAs are easily treated with available medical treatments, surgery, and sometimes radiotherapy. Nevertheless, gonadotroph adenomas lack medical therapeutic options, and treatment of aggressive PAs and pituitary carcinomas remains challenging. Here, we present an overview of the implications of the tumor microenvironment in PAs, reviewing its composition and function, as well as published cases that have been treated thus far using tumor microenvironment-targeting therapies. Additionally, we discuss emerging views, such as the concept of nonangiogenic tumors, and present perspectives regarding treatments that may represent future potential therapeutic options. Tumor-infiltrating lymphocytes, tumor-associated macrophages, folliculostellate cells, tumor-associated fibroblasts, angiogenesis, as well as the extracellular matrix and its remodeling, all have complex roles in the biology of PAs. They have been linked to hormone production/secretion, size, invasion, proliferation, progression/recurrence, and treatment response in PAs. From a therapeutic perspective, immune-checkpoint inhibitors and bevacizumab have already shown a degree of efficacy in aggressive PAs and pituitary carcinomas, and the use of numerous other tumor microenvironment-targeting therapies can be foreseen. In conclusion, similar to other cancers, understanding the tumor microenvironment improves our understanding of PA biology beyond genetics and epigenetics, and constitutes an important tool for developing future therapies.

中文翻译：

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垂体腺瘤中肿瘤微环境的生物学和治疗意义。

垂体腺瘤 (PA) 是源自垂体前叶腺内分泌细胞的肿瘤。大多数情况下，它们是良性肿瘤，但有时可能会出现侵袭性过程，并且在某些情况下会发生转移。他们的生物学，包括他们广泛的行为，只是部分了解。在治疗靶向方面，大多数 PA 很容易通过可用的药物治疗、手术，有时还可以进行放射治疗。然而，促性腺激素腺瘤缺乏医学治疗选择，侵袭性 PA 和垂体癌的治疗仍然具有挑战性。在这里，我们概述了 PA 中肿瘤微环境的影响，回顾了它的组成和功能，以及迄今为止使用肿瘤微环境靶向疗法治疗的已发表病例。此外，我们讨论了新出现的观点，例如非血管生成性肿瘤的概念，并提出了可能代表未来潜在治疗选择的治疗观点。肿瘤浸润淋巴细胞、肿瘤相关巨噬细胞、滤泡星状细胞、肿瘤相关成纤维细胞、血管生成以及细胞外基质及其重塑，在 PA 的生物学中都具有复杂的作用。它们与 PA 中的激素产生/分泌、大小、侵袭、增殖、进展/复发和治疗反应有关。从治疗的角度来看，免疫检查点抑制剂和贝伐珠单抗已经在侵袭性 PA 和垂体癌中显示出一定程度的疗效，并且可以预见许多其他肿瘤微环境靶向疗法的使用。总之，与其他癌症相似，