ISSN: 2155-9899
Ning-Sun Yang, Sheng-Yen Lin, Ying-Chu Wang, Chun-Wen Lan, Wen-Chin Yang, Pei-Wen Hsiao and Wen-Chi Wei
Accepted Abstracts: J Clin Cell Immunol
M yeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells including immature granulocytes, macrophages, and dendritic cells that expand extensively during cancer, inflammation and infection. MDSCs are increasingly recognized as having a crucial role in protecting tumor cells from immune surveillance by suppressing anti-tumor immunity. This study aimed to investigate the immune-regulatory and antitumor activities of TMP1 on MDSC expansion and tumor metastasis. The results showed that TMP1 effectively suppressed mammary 4T1 tumor metastasis and increased mouse survival in a mammary tumor resection mouse model. In addition, TMP1 significantly decreased tumor- induced splenomegaly and the number of granulocytic MDSCs in test mice. In ex vivo cell culture assays, TMP1 did not decrease the level of granulocyte colony stimulating factor (G-CSF, a key cytokine for granulocytic MDSC differentiation) produced by tumor tissue, tumor associated stromal cells and 4T1 cells. However, TMP1 significantly inhibited granulocyte- macrophage colony stimulating factor (GM-CSF) or G-CSF-induced MDSC differentiation from bone marrow cells. TMP1 also strongly inhibited GM-CSF-induced expression level of G-CSF receptor in bone marrow cells. Taken together, our results suggest that TMP1 significantly suppresses mammary tumor metastasis via inhibition of granulocytic MDSC differentiation.