Abstract
Regulatory T cells (Tregs) are physiologically designed to prevent autoimmune disease and maintain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA expressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the im-munosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lymphocytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibition of Lck and inactivation of Zap-70, an increase in the Foxp3 methylation status and, ultimately, the reduced production of suppressive cytokines. These results indicate a role of MGL as an immunomodulator within the tumour microenvironment interfering with Treg functions, suggesting its possible use in the design of anticancer vaccines.
Highlights
Regulatory T cells (Tregs) (CD4+CD25+FOXP3+) play an essential role in the control of the immune response
macrophage galactose-type C-type lectin (MGL) binding to CD45RA expressed by Treg cells was performed using a recombinant protein of MGL. rhMGL-Fc was made up of the extracellular domain of MGL fused to Fc domain of a human IgG1
Able to inhibit the anti-tumour function of specific T cells; their presence in tumour is directly related to poor prognosis [15]
Summary
Regulatory T cells (Tregs) (CD4+CD25+FOXP3+) play an essential role in the control of the immune response. Tregs represent one of the main cellular subsets of the regulative network that are found in tumour microenvironments and are shown to be responsible for the negative regulation that occurs during antitumor immune responses [2]. This population exerts its regulatory activity through cell-cell contact and by producing suppressive factors such as interleukin (IL)-10 and Tumour Growth Factor (TGF)-ß. Several reports have shown that their presence in tumours is strongly related to the stage of disease and influences the outcome of the disease and therapy
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