Page 54 - D. Cancer biology

[D. Cancer biology-40]

Hes1 in myeloid cells promotes tumor immune tolerance

through regulation of Arg-1

Hyeok Gu Kang¹˙², Kyung-Hee Chun¹˙²

¹Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 03722, South Korea, ²Brain

Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, South Korea

Substantial clinical and experimental evidence indicates that macrophages present abundantly in most tumor types
and have a major regulatory role in promoting tumor progression to malignancy. Previously, Notch signaling is

critical in functioning macrophages and recently, it has been reported that Notch signaling is important in tumor

associated macrophages (TAM) differentiation. We analyzed Notch signaling related genes in TAM using public data
set and MMTV-PyMT mouse TAM. And we found that Hes1 is up-regulated in TAM compared with other tissue
macrophages. Next we observed that tumor soluble factor and IL-4 increase Hes1 expression level, but not hypoxia.

By crossing LysM-Cre and Hes1 floxed mice, we achieved specific deletion of Hes1 in myeloid cells. Subcutaneously
injected tumor cells display retardation of tumor growth in Hes1 cKO mice. Hes1 deficiency in the myeloid

compartment increase infiltration of T cells and NK cells in Tumor. Additionally, MDSC in bone marrow and spleen
are reduced in Hes1 cKO mice compared to WT. Ablation of Hes1 in myeloid cells decreased intracellular expression

of the anti-inflammatory marker Arg-1 in TAM. These results indicate that anti-tumor effects of Hes1 deficient
macrophage may be from reduction of Arg-1 expression.