工程化小鼠模型中的免疫龛形成揭示肿瘤休眠机制

Residual tumor cells can persist in a dormant state during clinical remissions that may last decades. The mechanisms that lead to such growth control vs. eventual reactivation and macroscopic tumor outgrowth remain unclear.

Here, we report data from a mouse model that reveals a key role of host immunity and the cellular and molecular mechanisms that control tumor dormancy. Abrogation of myeloid-specific TGF- RII expression (T RII myeKO ) resulted in an IFN- rich immune microenvironment.

IFN- in turn elevated KLF4-mediated SLURP1 production in malignant cells, which is critical to the tumor cell quiescent state through interruption of fibronectin-integrin signaling pathways. The dormant tumor lesions were located in spatially localized immune niches rich in NK cells, cDCs, monocytes, and neutrophils, concomitant with tumor cell inactivation of NK cell immune surveillance through a CD200-CD200R1 mechanism.

Our studies identify the IFN- -KLF4-SLURP1 and CD200-CD200R1 axes as critical molecular drivers in tumor dormancy regulated by immune-tumor crosstalk. These insights provide enhanced mechanistic understanding of tumor dormancy in a mouse model suitable for further investigation of cancer treatment resistance and prevention of metastatic spread.