Although the dichotomous role of macrophages in cancer (promote or suppress it) is well documented (reviews, [49,50,51]), the new information here is threefold: (i) the status of a stress-inducible master-switch gene Atf3 plays a pivotal role; (ii) the dichotomy is manifested under the treatment of cyclophosphamide, a frontline chemotherapeutic agent; (iii) the antimicrobial genes are likely a part of the transcriptional program associated with anti-cancer activities. The gene discussed is ATF3; the disease is cancer.