Myeloid cells are the most abundant hematopoietic cells in the human body and play a crucial role in tumor angiogenesis, invasion, and metastasis. Here we found that deletion of the gene encoding TGFβ receptor 2 (Tgfbr2) specifically in myeloid cells reduced the level of platelet factor-4 (PF4) in the myeloid cells of 4T1 tumor bearing mice. This is accompanied by decreased lung metastasis of 4T1 mammary carcinoma. Interestingly, deletion of Cxcr3, encoding the receptor for PF4, significantly decreased the lung metastasis of 4T1 mammary carcinoma. The decreased metastasis may attribute to augmented anti-immunity. First, myeloid cells with Cxcr3 deletion showed decreased expression of IL-10, IL-4, iNOs, and arginase. In addition, there was an increased number of both CD4+ and CD8+ T cell in Cxcr3-/- mice compared to the wilt type controls. Our results suggest that TGFβ regulation of PF4 may modulate cancer metastasis through suppressing host anti-tumor immunity.

Citation Format: Yanli Pang, Guiquan Zhu, Li Yang. Myeloid TGF-β signaling regulates Platelet factor 4 expression that is important in host immune suppression and tumor metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1435. doi:10.1158/1538-7445.AM2013-1435