IL-6 regulates CCR5 expression and immunosuppressive capacity of MDSC in murine melanoma

• DOI: 10.1136/jitc-2020-000949
• Publication Date: 2020-08-12T14:07:48Z
• Authors: Rebekka Weber; Zeno Riester; Laura Hüser; Carsten Sticht; Alina Siebenmorgen; Christopher Groth; Xiaoying Hu; Peter Altevogt; Jochen S Utikal; Viktor Umansky
• Keywords: Myeloid-derived Suppressor Cell; CCL5

Background Myeloid-derived suppressor cells (MDSC) play a major role in the immunosuppressive melanoma microenvironment. They are generated under chronic inflammatory conditions characterized by constant production of cytokines, chemokines and growth factors, including IL-6. Recruitment MDSC to tumor is mediated interaction between chemokine receptors, particular C–C receptor (CCR)5. Here, we studied mechanisms CCR5 upregulation increased function + MDSC. Methods The immortalized myeloid cell line MSC-2, primary immature vitro differentiated were used determine factors molecular regulating expression markers at mRNA protein levels. relevance identified pathways was validated on RET transgenic mouse model, which also target vivo. Results IL-6 upregulated arginase 1 STAT3-dependent mechanism. presence strongly inhibited CD8 T functions compared with without A correlation levels, phosphorylated STAT3 tumor-infiltrating demonstrated model. Surprisingly, overexpressing tumors grew significantly slower mice accompanied activation. Moreover, melanoma-bearing treated blocking antibodies showed accelerated development. Conclusion Our ex vivo findings that induced strong activity MDSC, highlighting this cytokine as promising for immunotherapy. However, therapy did not prove be effective but rather aggravated progression. Further studies needed identify combination therapies, cancer entities or patient subsets benefit from anti-IL-6 treatment.