The transient metabolic switch in monocytes and macrophages in the peritumoral stroma induced sustained expression of CA12 on these cells through HIF1α- and autocrine cytokine-dependent pathways, and importantly, targeting CA12 could selectively regulate the accumulation and function of macrophages in tumor tissue and induce tumor regression in a mouse model alone or in synergistic combination with immune-checkpoint blockade. The gene discussed is HIF1A; the disease is neoplasm.