Molecular mechanisms that regulate tumor-associated macrophage (TAM) phenotype and function are incompletely understood. The pseudokinase TRIB1 has been reported as a regulator of macrophage phenotypes, both in mouse and human systems. Bioinformatic analysis was used to investigate the link between expression in breast cancer and therapeutic response to chemotherapy. models of breast cancer included immune-competent mice to characterize the consequences of altered (reduced or elevated) myeloid expression on tumor growth and composition of stromal immune cell populations. TRIB1 was highly expressed by TAMs in breast cancer and high expression correlated with response to chemotherapy and patient survival. Both overexpression and knockout of myeloid promote mouse breast tumor growth, albeit through different molecular mechanisms. Myeloid deficiency led to an early acceleration of tumor growth, paired with a selective reduction in perivascular macrophage numbers and enhanced oncogenic cytokine expression . In contrast, elevated levels of in myeloid cells led to an increased late-stage mammary tumor volume, coupled with a reduction of NOS2 expressing macrophages and an overall reduction of macrophages in hypoxic tumor regions. In addition, we show that myeloid is a previously unknown, negative regulator of the anti-tumor cytokine IL-15, and that increased myeloid expression leads to reduced IL-15 levels in mammary tumors, with a consequent reduction in the number of T-cells that are key to anti-tumor immune responses. Together, these results define a key role for TRIB1 in chemotherapy responses for human breast cancer and provide a mechanistic understanding for the importance of the control of myeloid TRIB1 expression in the development of this disease.