CKLF instigates a "cold" microenvironment to promote MYCN-mediated tumor aggressiveness.

Autor: Qin X; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Lam A; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Zhang X; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, China., Sengupta S; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Iorgulescu JB; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Molecular Diagnostics Laboratory, Department of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ni H; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Das S; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; School of Biotechnology, KIIT University, Bhubanesw, India., Rager M; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Zhou Z; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Zuo T; Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, MA, USA., Meara GK; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Floru AE; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Kemet C; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Veerapaneni D; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Kashy D; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Lin L; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Lloyd K; Institute for Protein Innovation, Boston, MA, USA., Kwok L; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Smith KS; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Nagaraju RT; Faculty of Biology, Medicine and Health, Division of Cancer Sciences, University of Manchester, Manchester, UK.; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK., Meijers R; Institute for Protein Innovation, Boston, MA, USA., Ceol C; Department of Molecular, Cell and Cancer Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA., Liu CT; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Alexandrescu S; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Keskin DB; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.; Department of Computer Science, Metropolitan College, Boston University, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., George RE; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Feng H; Departments of Pharmacology, Physiology & Biophysics and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Mar 15; Vol. 10 (11), pp. eadh9547. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1126/sciadv.adh9547
Abstrakt: 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. Genetic depletion of CD4 + T regulatory cells abolishes the immunorestrictive and protumorigenic effects of CKLF. Our work supports that disrupting CKLF-mediated cross-talk between tumor and CD4 + suppressor cells represents a promising immunotherapeutic approach to battling MYCN-driven tumors.
Databáze: MEDLINE