Abstract: The present invention is based, in part, on the discovery of anti-VSIG4 composition (e.g., monoclonal antibodies and antigen-binding fragments thereof), that regulate myeloid cell inflammatory phenotypes, such as suppressive myeloid cells, monocytes, macrophages, neutrophils, and/or dendritic cells, including polarization, activation, and/or function, and methods of using such anti-VSIG4 compositions for therapeutic, diagnostic, prognostic, and screening purposes.