Loading…
Mesenchymal Stem Cells Induce an Immunosuppressive Microenvironment in Pituitary Tumors
Abstract Context The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSCs) and immune cells, among others. MSC have been isolated from different tumors and they favor tumor cell growth; however, their role in pituitary tumors (PTs) remains unknown. O...
Saved in:
Published in: | The journal of clinical endocrinology and metabolism 2024-10, Vol.109 (11), p.2943-2955 |
---|---|
Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Abstract
Context
The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSCs) and immune cells, among others. MSC have been isolated from different tumors and they favor tumor cell growth; however, their role in pituitary tumors (PTs) remains unknown.
Objective
Herein we report the presence of MSCs in 2 adrenocorticotropin (ACTH)-secreting PTs causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF), and 2 nontumoral pituitary glands (MS).
Methods
We have analyzed the transcriptomic profiles by RNA sequencing and compared MSCs in terms of their immunosuppressive effects against lymphoid T-cell and macrophage populations by means of cocultures and flow cytometry.
Results
Our transcriptomic analysis revealed molecular differences between MSCs derived from nontumoral pituitaries and MSCs derived from PTs. Two distinct subpopulations of MSC emerged: one displaying immunosuppressive properties and the other with increased proproliferative capabilities, regardless of their origin. MSCs derived from ACTH- and nonfunctioning PTs, but not those derived from nontumoral glands, significantly inhibited the proliferation of activated T cells, favored the generation of regulatory T cells, and promoted M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony-stimulating factor (M-CSF) and interleukin-10. Importantly, MSC derived from ACTH-PTs showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors.
Conclusion
This study demonstrates the presence of at least 2 MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSCs may have important implications in PT growth. |
---|---|
ISSN: | 0021-972X 1945-7197 1945-7197 |
DOI: | 10.1210/clinem/dgae212 |