title: In vitro evidence of the presence of mesenchymal stromal cells in cervical cancer and their role in protecting cancer cells from cytotoxic T cell activity.
abstract: Mesenchymal stromal cells (MSCs) have been isolated from different tumors and it has been suggested that they support tumor growth through immunosuppression processes that favor tumor cell evasion from the immune system. To date, however, the presence of MSCs in cervical cancer (CeCa) and their possible role in tumor growth remains unknown. Herein we report on the presence of MSCs in cervical tissue, both in normal conditions (NCx-MSCs) and in CeCa (CeCa-MSCs), and described several biological properties of such cells. Our study showed similar patterns of cell surface antigen expression, but distinct differentiation potentials, when we compared both cervical MSC populations to MSCs from normal bone marrow (BM-MSCs, the gold standard). Interestingly, CeCa-MSCs were negative for the presence of human papilloma virus, indicating that these cells are not infected by such a viral agent. Also, interestingly, and in contrast to NCx-MSCs, CeCa-MSCs induced significant downregulation of surface HLA class I molecules (HLA-A*0201) on CaSki cells and other CeCa cell lines. We further observed that CeCa-MSCs inhibited antigen-specific T cell recognition of CaSki cells by cytotoxic T lymphocytes (CTLs). HLA class I downregulation on CeCa cells correlated with the production of IL-10 in cell cocultures. Importantly, this cytokine strongly suppressed recognition of CeCa cells by CTLs. In summary, this study demonstrates the presence of MSCs in CeCa and suggests that tumor-derived MSCs may provide immune protection to tumor cells by inducing downregulation of HLA class I molecules. This mechanism may have important implications in tumor growth.
authors: Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City, Mexico.
authors: Juan J
authors: JJ
authors: Montesinos
authors: María de L
authors: Mde L
authors: Mora-García
authors: Héctor
authors: H
authors: Mayani
authors: Eugenia
authors: E
authors: Flores-Figueroa
authors: Rosario
authors: R
authors: García-Rocha
authors: Guadalupe R
authors: GR
authors: Fajardo-Orduña
authors: Marta E
authors: ME
authors: Castro-Manrreza
authors: Benny
authors: B
authors: Weiss-Steider
authors: Alberto
authors: A
authors: Monroy-García
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology*; D015536:Down-Regulation; D005260:Female; D015789:HLA-A2 Antigen / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D027383:Papillomaviridae; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016753:Interleukin-10
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