In this study, we wanted to investigate more about the mechanisms involved in the immunosuppressive activity of tumor-MSCs. First, we observed that T cells infiltrating HNSCC were enriched for Treg, however, most of the effector T cells were characterized by IFN-γ and TNF-α production. Looking at the effect of these two cytokines on MSCs, we found out that upon inflammatory stimulation, MSCs upregulate the expression of immunosuppressive molecules such as IDO1, IL4I1 and PD-L1. Testing the functional role of anyone of these molecules, we discovered that IDO1 was the major player in MSCs’ mediated immunosuppression, but also IL4I1 and PD-L1 play a small part. We also found out that, MSCs are able to attract (by the expression of numerous chemokines) and bind lymphocytes (by expressing CD106), nevertheless their inhibitory action does not seem to be due to cellular contact. Our data together with the previous ones, consolidate the hypothesis that tumor-MSCs could promote tumor growth, directly or indirectly inhibiting the immune response.
Meccanismi cellulari e molecolari coinvolti nell’evasione dall’immunosorveglianza nei carcinomi testa-collo a cellule squamose (Cellular and molecular mechanisms of immunosurveillance escape in Head Neck Squamous Cell Carcinoma) / Gianni Montaini. - (2019).
Meccanismi cellulari e molecolari coinvolti nell’evasione dall’immunosorveglianza nei carcinomi testa-collo a cellule squamose (Cellular and molecular mechanisms of immunosurveillance escape in Head Neck Squamous Cell Carcinoma)
Gianni Montaini
Writing – Original Draft Preparation
2019
Abstract
In this study, we wanted to investigate more about the mechanisms involved in the immunosuppressive activity of tumor-MSCs. First, we observed that T cells infiltrating HNSCC were enriched for Treg, however, most of the effector T cells were characterized by IFN-γ and TNF-α production. Looking at the effect of these two cytokines on MSCs, we found out that upon inflammatory stimulation, MSCs upregulate the expression of immunosuppressive molecules such as IDO1, IL4I1 and PD-L1. Testing the functional role of anyone of these molecules, we discovered that IDO1 was the major player in MSCs’ mediated immunosuppression, but also IL4I1 and PD-L1 play a small part. We also found out that, MSCs are able to attract (by the expression of numerous chemokines) and bind lymphocytes (by expressing CD106), nevertheless their inhibitory action does not seem to be due to cellular contact. Our data together with the previous ones, consolidate the hypothesis that tumor-MSCs could promote tumor growth, directly or indirectly inhibiting the immune response.File | Dimensione | Formato | |
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Tesi Gianni Montaini Finale.pdf
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