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The synergistic interaction between the calcineurin B subunit and IFN-? enhances macrophage antitumor activity.

ABSTRACT: Macrophages 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-? to make macrophages highly cytotoxic to cancer cells. Furthermore, CnB and IFN-? 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 ?M-p38 MAPK signaling and IFN-?-initiated p38/PKC-?/Jak2 signaling. Interestingly, the signal transducer and activator of transcription 1 (STAT1) is a key factor that orchestrates the synergy of CnB and IFN-?, and the phosphorylation status at Ser727 and Tyr701 of STAT1 is directly regulated by CnB and IFN-?.

SUBMITTER: Su Z

PROVIDER: S-EPMC4669720 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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The synergistic interaction between the calcineurin B subunit and IFN-γ enhances macrophage antitumor activity.

Su Z Z Yang R R Zhang W W Xu L L Zhong Y Y Yin Y Y Cen J J DeWitt J P JP Wei Q Q

Cell death & disease 20150507

Macrophages 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 mo ...[more]

PMID: 25950470

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