Oncogenic transformation tunes the cross-talk between mesenchymal stem cells and T lymphocytes.
Stem cells from mesenchymal origin (MSC) exert a plethora of immunomodulatory effects. We created a neoplastic model based on in vitro step-wise transformation to assess whether oncogenic pathways have the capacity to mould the cross-talk of MSC and lymphocytes. Neoplastic MSC exhibit an increased inhibitory effect on T cell proliferation, either directly or mediated by myeloid derived suppressor cells. Additionally, transformation of MSC enhances T cell apoptosis without reducing either the percentage of CD25 expressing cells or the level of this protein expression. Malignant transformation drives MSC to lose dependency on nitric oxide for immunosuppression whilst increasing the constitutive production of PGE2. Our results indicate that oncogenesis tunes the interplay between MSC and immune cells, favoring cancer immune evasion.
Tumor Immunology Direction, Havana, Cuba; Center of Molecular Immunology, Havana, Cuba.
Nilda
N
Sánchez
Tumor Immunology Direction, Havana, Cuba; Center of Molecular Immunology, Havana, Cuba.
Alex
A
Miranda
Cancer Institute, University College of London, Gower Street, London WC1E 6BT, UK.
Juan M
JM
Funes
Immunobiology Direction, Havana, Cuba; Center of Molecular Immunology, Havana, Cuba.
Giselle
G
Hevia
Center of Molecular Immunology, Havana, Cuba.
Rolando
R
Pérez
Tumor Immunology Direction, Havana, Cuba; Center of Molecular Immunology, Havana, Cuba. Electronic address: yoel@cim.sld.cu.
Joel
J
de León
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D053645:Interleukin-2 Receptor alpha Subunit; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015232:Dinoprostone
Immunosuppression; Lymphocytes; Mesenchymal stem cells; Oncogenic transformation