Mesenchymal stromal cells promote B-cell lymphoma in lacrimal glands by inducing immunosuppressive microenvironment
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Min Joung Lee1, Se Yeon Park2, Jung Hwa Ko2, Hyun Ju Lee2, Jin Suk Ryu2, Jong Woo Park2, Sang In Khwarg3, Sun-Ok Yoon4 and Joo Youn Oh2,3
1Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Korea
2Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
3Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea
4R & D Lab, Eutilex Co., Ltd, Seoul, Korea
Joo Youn Oh, email: [email protected]
Sun-Ok Yoon, email: [email protected]
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
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.
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