Mesenchymal stromal cells promote B-cell lymphoma in lacrimal glands by inducing immunosuppressive microenvironment

// Min Joung Lee 1 , Se Yeon Park 2 , Jung Hwa Ko 2 , Hyun Ju Lee 2 , Jin Suk Ryu 2 , Jong Woo Park 2 , Sang In Khwarg 3 , Sun-Ok Yoon 4 and Joo Youn Oh 2, 3 1 Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Korea 2 Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea 3 Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea 4 R & D Lab, Eutilex Co., Ltd, Seoul, Korea Correspondence to: Joo Youn Oh, email: jooyounoh77@gmail.com Sun-Ok Yoon, email: syoon75@gmail.com Keywords: apoptosis, B cell lymphoma, lacrimal gland, mesenchymal stromal cells, myeloid-derived suppressor cell Received: December 01, 2016     Accepted: July 18, 2017     Published: August 07, 2017 ABSTRACT Mesenchymal stromal cells (MSCs) have therapeutic potential for various diseases because of their anti-inflammatory and immunosuppressive properties. However, the immunosuppressive microenvironment allows tumor cells to evade immune surveillance, whereas maintenance of inflammation is required for tumor development and progression. Hence, MSCs may promote or suppress tumors in a context-dependent manner. We here investigated the effects of bone marrow-derived MSCs in a murine model of lacrimal gland B-cell lymphoma. Co-injection of MSCs with B lymphoma cells enhanced tumor growth in lacrimal glands without long-term engraftment. Of note, MSCs induced greater infiltration of immune and immune-regulatory cells near tumor: CD4 + cells, CD11b + cells, CD4 + Foxp3 + regulatory T cells and CD11b + Ly6C + Ly6G − myeloid-derived suppressor cells. Concurrently, there was up-regulation of immune-related molecules including TNF-α, IL-1β, TGF-β1, and arginase in glands treated with MSCs. Apoptosis in tumor was less severe in mice treated with MSCs compared to those without MSCs; however, MSCs did not directly inhibit apoptosis of B lymphoma cells in an in vitro co-culture. Together, data demonstrate that MSCs create immunosuppressive milieu by recruiting regulatory immune cells and promote B-cell lymphoma growth in lacrimal glands.