Tumor-associated macrophages (TAMs) represent the most abundant hematopoietic cell type in the solid tumor microenvironment. TAMs drive T cell inhibition, promote angiogenesis, and produce tumor growth factors. Although they can paradoxically exert antitumor activity and prime protective immunity, the pathways driving this phenotype remain unclear. In this issue of the JCI, Liu and colleagues identified the c-Maf transcription factor as a master regulator of protumoral TAM polarization. The authors found that c-Maf promoted TAMs’ immunosuppressive activity, governed their metabolic programming, and drove expression of the macrophage differentiation protein, CSF1R. Further, inhibiting c-Maf in myeloid progenitors, and consequent myeloid-lineage cells, including TAMs, delayed tumor growth. Importantly, β-glucan treatment reduced c-MAF expression in macrophages and monocytes from patients with non–small cell lung cancer (NSCLC) where c-MAF is overexpressed. These results reveal mechanisms whereby myeloid cells drive human cancer progression by thwarting protective immunity and could lead to immunotherapy for most solid malignancies.

肿瘤相关巨噬细胞（TAM）代表实体肿瘤微环境中最丰富的造血细胞类型。TAM驱动T细胞抑制，促进血管生成，并产生肿瘤生长因子。尽管它们可以自相矛盾地发挥抗肿瘤活性和主要的保护性免疫，但驱动该表型的途径仍不清楚。在本期JCI中，Liu及其同事确定了c-Maf转录因子是肿瘤TAM极化的主要调节因子。作者发现c-Maf可以促进TAMs的免疫抑制活性，控制其代谢程序，并驱动巨噬细胞分化蛋白CSF1R的表达。此外，抑制髓样祖细胞中的c-Maf及其随后的髓样谱系细胞（包括TAM）会延迟肿瘤的生长。重要的，β-葡聚糖治疗可降低c-MAF过表达的非小细胞肺癌（NSCLC）患者巨噬细胞和单核细胞中c-MAF的表达。这些结果揭示了髓样细胞通过阻止保护性免疫来驱动人类癌症进展并可能导致大多数实体恶性肿瘤的免疫疗法的机制。