WNT11 and CytoF data

Liver metastasis (LM) poses a significant challenge in cancer treatment, with limited therapeutic options and poor prognosis. Understanding the tumor microenvironment (TME) dynamics and immune interactions is crucial for developing effective treatments. Here, we found that WNT11 promoted CD8+ T cell exclusion and suppression and correlated with poor prognosis in liver metastases. Mechanistically, WNT11-overexpressing tumor cells directly reduced CD8+ T cell recruiting and activity via decreasing CXCL10 and CCL4 expression through CAMKII-mediated β-catenin/AFF3 downregulation. Otherwise, WNT11-overexpressing tumor cells promoted immunosuppressive macrophage polarization by inducing IL17D expression via CAMKII/NFκB pathway, which leading to CD8+ T cell suppression. Moreover, CAMKII inhibition potentiated the efficacy of anti-PD-1 therapy in mouse liver metastasis model. Serum WNT11 was identified as a potential minimally invasive biomarker in the management of CRC-LM with immunotherapy. Our findings highlight WNT11/CAMKII axis as a critical regulator of TME and a promising target for immunotherapy in liver metastasis.