CKLF instigates a “cold” microenvironment to promote MYCN-mediated tumor aggressiveness

• DOI: 10.1126/sciadv.adh9547
• Publication Date: 2024-03-15T17:58:37Z
• Authors: 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. Na...; Rob Meijers; Craig Ceol; Ching-Ti Liu; Sanda Alexandrescu; Catherine J. Wu; Derin B. Keskin; Rani E. George; Hui Feng
• Keywords: Immunosuppression

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 tackle problem. We found that chemokine-like factor ( CKLF ) is highly expressed by various solid tumor cells transcriptionally up-regulated MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated early premalignant stage, secrete attract CCR4-expressing CD4 + cells, inducing immunosuppression aggression. Genetic depletion of T regulatory abolishes immunorestrictive protumorigenic effects CKLF. Our work supports disrupting CKLF-mediated cross-talk between suppressor represents promising immunotherapeutic approach battling tumors.