THU499 The Mesenchymal Stem Cells Induce Immunosuppressive Microenvironment In Pituitary Tumors

Abstract

Abstract Disclosure: D. Marrero-Rodríguez: None. V. Cortes-Morales: None. K. Taniguchi-Ponciano: None. A. Valenzuela-Perez: None. S. Vela-Patiño: None. A. Cano-Zaragoza: None. F. Martinez-Mendoza: None. J. Kerbel: None. S. Andonegui-Elguera: None. J. Montesinos: None. M. Mercado: None. The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSC) and immune cells. MSC are a subset of heterogeneous cell populations characterized by the expression of CD105, CD73, and CD90 that can differentiate into chondrocytes, osteoblasts, and adipocytes in vitro. They are known to have immunomodulatory capabilities. Our aim was to isolate and characterize the immunomodulatory capabilities of MSC from pituitary tumors (PT) and non-tumoral gland as well as to describe the immune TME. We isolated and cultivated MSC from LH/FSH-PT and ACTH-PT, as well as non-tumoral pituitary glands. The MSC obtained from PT and non-tumoral gland were co-cultured in the presence of monocytes from healthy donors and their ability to transform into M0, M1 or M2 macrophages was assessed by flow cytometry. The results showed that pituitary tumors derived MSC induce an immunosuppressive M2 macrophage state, by increasing the expression of CD14 and CD206 markers, and decreasing HLA-DR. Upon co-culturing them with naïve T cells, PT MSC were capable inducing a Treg phenotype. To identify PT TME, we performed tumor whole transcriptome characterization and cellular deconvolution using CIBERSORT. Our analysis was indicative of a strong presence of M2 macrophages, TCD4+ and TCD8+ cells, which was confirmed by immunofluorescence, suggesting an immunosuppressive TME. Thus, the MSC immunosuppressive induction correlates directly with immune TME. ACTH-PT derived MSC showed a stronger anti-inflammatory activity than LH/FSH-PT. We also characterized the transcriptomic differences between non-tumoral and PT derived MSC by means of RNAseq. We found differences between the non-tumoral MSC and pituitary tumor derived MSC, but mainly between ACTH- and LH/FSH-PT derived MSC. In conclusion our data suggest that the presence of MSC influence an immunosuppressive tumor microenvironment alongside with tumor cells. Presentation: Thursday, June 15, 2023