The effects of neoadjuvant chemotherapy (NACT) on innate antitumor immunity are not fully understood. Heath et al. find that NACT promotes tumor-associated macrophages (TAM) to acquire an antitumor phenotype in high-grade serous ovarian cancer (HGSOC). Although TAM density is reduced with NACT, the treatment also decreases expression of M2-related markers while increasing proinflammatory pathways, including the inflammasome. These TAMs are found to be important for disease-free and overall survival in orthotopic HGSOC models. The data highlight the potential of targeting tumor-promoting TAMs whilst augmenting the activity of antitumor TAMs to boost therapeutic responses in the context of NACT. Read more in this issue on page 665. Original image from Fig. 1C. Artwork by Lewis Long.