免疫生态位形成揭示肿瘤休眠机制和靶向机会

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

Here, we report abrogation of myeloid TGF- RII resulted in an IFN- rich microenvironment. IFN- in turn elevated KLF4-mediated SLURP1 production in malignant cells, which is critical to their quiescent state through interruption of fibronectin-integrin pathways. The dormant tumor lesions were found in spatially localized immune niches rich in NK cells, cDCs, monocytes, and neutrophils, concomitant with tumor cell inactivation of NK cell immune surveillance through CD200-CD200R1.

Our studies identify the IFN- -KLF4-SLURP1 and CD200-CD200R1 axes as critical molecular drivers in tumor dormancy regulated by immune-tumor crosstalk. Targeting the CD200-mediated dormant niche in combination with chemotherapy and immune check point blockade (ICB) significantly eradicated the dormant tumor cells. These insights provide mechanistic understanding of tumor dormancy and treatment options for ICB relapse.