Xiaodan Qin, Andrew Lam, Xu Zhang, Satyaki Sengupta, J Bryan Iorgulescu, Hongru Ni, Sanjukta Das, Madison Rager, Zhenwei Zhou, Tao Zuo, Grace K Meara, Alexander E Floru, Chinyere Kemet, Divya Veerapaneni, Daniel Kashy, Liang Lin, Kenneth Lloyd, Lauren Kwok, Kaylee S Smith, Raghavendar T Nagaraju, Rob Meijers, Craig Ceol, Ching-Ti Liu, Sanda Alexandrescu, Catherine J Wu, Derin B Keskin, Rani E George, Hui Feng
Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor ( CKLF ) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated that as early as the premalignant stage, tumor cells secrete CKLF to attract CCR4-expressing CD4+ cells, inducing immunosuppression and tumor aggression...
March 15, 2024: Science Advances