Tumor-associated macrophages (TAMs) are a heterogenous population of myeloid cells that dictate the inflammatory tone of the tumor microenvironment (TME). In this study, we unveiled a mechanism by which scavenger receptor CD36 suppresses TAM inflammatory states. CD36 was upregulated in TAMs and associated with immunosuppressive features, and myeloid-specific deletion of CD36 significantly reduced tumor growth. Moreover, CD36-deficient TAMs acquired inflammatory signatures including elevated type-I interferon (IFN-I) production, mirroring the inverse correlation between CD36 and IFN-I response observed in cancer patients. IFN-I, especially IFNβ, produced by CD36-deficient TAMs directly induced tumor cell quiescence and delayed tumor growth. Mechanistically, CD36 acted as a natural suppressor of IFN-I signaling in macrophages through p38 activation downstream of oxidized lipid signaling. These findings establish CD36 as a critical regulator of TAM function and the tumor inflammatory microenvironment, providing additional rationale for pharmacological inhibition of CD36 to rejuvenate anti-tumor immunity.

中文翻译：

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肿瘤相关巨噬细胞中的清道夫受体 CD36 通过抑制 I 型干扰素信号传导促进癌症进展


肿瘤相关巨噬细胞 （TAM） 是异质性髓系细胞群，决定肿瘤微环境 （TME） 的炎症基调。在这项研究中，我们揭示了清道夫受体 CD36 抑制 TAM 炎症状态的机制。CD36 在 TAMs 中上调并与免疫抑制特征相关，CD36 的髓系特异性缺失显着减少了肿瘤生长。此外，CD36 缺陷的 TAM 获得了炎症特征，包括 I 型干扰素 （IFN-I） 产生增加，反映了在癌症患者中观察到的 CD36 和 IFN-I 反应之间的负相关。CD36 缺陷型 TAM 产生的 IFN-I，尤其是 IFNβ，直接诱导肿瘤细胞静止并延迟肿瘤生长。从机制上讲，CD36 通过氧化脂质信号转导下游的 p38 激活，在巨噬细胞中充当 IFN-I 信号转导的天然抑制因子。这些发现确立了 CD36 是 TAM 功能和肿瘤炎症微环境的关键调节因子，为药理学抑制 CD36 以恢复抗肿瘤免疫提供了额外的理由。