Su, ZYang, RZhang, WXu, LZhong, YYin, YCen, JDeWitt, J PWei, Q2016-01-042015Su, Z, R Yang, W Zhang, L Xu, Y Zhong, Y Yin, J Cen, J P DeWitt, and Q Wei. 2015. “The synergistic interaction between the calcineurin B subunit and IFN-γ enhances macrophage antitumor activity.” Cell Death & Disease 6 (5): e1740. doi:10.1038/cddis.2015.92. http://dx.doi.org/10.1038/cddis.2015.92.2041-4889http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993498Macrophages are involved in tumor growth and progression. They infiltrate into tumors and cause inflammation, which creates a microenvironment favoring tumor growth and metastasis. However, certain stimuli may induce macrophages to act as tumor terminators. Here we report that the calcineurin B subunit (CnB) synergizes with IFN-γ to make macrophages highly cytotoxic to cancer cells. Furthermore, CnB and IFN-γ act synergistically to polarize mouse tumor-associated macrophages, as well as human monocyte-derived macrophages to an M1-like phenotype. This synergy is mediated by the crosstalk between CnB-engaged integrin αM-p38 MAPK signaling and IFN-γ-initiated p38/PKC-δ/Jak2 signaling. Interestingly, the signal transducer and activator of transcription 1 (STAT1) is a key factor that orchestrates the synergy of CnB and IFN-γ, and the phosphorylation status at Ser727 and Tyr701 of STAT1 is directly regulated by CnB and IFN-γ.en-USJournal Article2016-01-0410.1038/cddis.2015.92