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CKLF instigates a "cold" microenvironment to promote MYCN-mediated tumor aggressiveness.
Qin, Xiaodan; Lam, Andrew; Zhang, Xu; Sengupta, Satyaki; Iorgulescu, J Bryan; Ni, Hongru; Das, Sanjukta; Rager, Madison; Zhou, Zhenwei; Zuo, Tao; Meara, Grace K; Floru, Alexander E; Kemet, Chinyere; Veerapaneni, Divya; Kashy, Daniel; Lin, Liang; Lloyd, Kenneth; Kwok, Lauren; Smith, Kaylee S; Nagaraju, Raghavendar T; Meijers, Rob; Ceol, Craig; Liu, Ching-Ti; Alexandrescu, Sanda; Wu, Catherine J; Keskin, Derin B; George, Rani E; Feng, Hui.
Affiliation
  • 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.
  • Sengupta S; Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, China.
  • Iorgulescu JB; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Ni H; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Das S; Molecular Diagnostics Laboratory, Department of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 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 Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zuo T; School of Biotechnology, KIIT University, Bhubanesw, India.
  • 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; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Kemet C; Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, 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; 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.
  • Lloyd K; 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.
  • 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; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Nagaraju RT; Institute for Protein Innovation, Boston, MA, USA.
  • Meijers R; 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.
  • Ceol 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.
  • Liu CT; Faculty of Biology, Medicine and Health, Division of Cancer Sciences, University of Manchester, Manchester, UK.
  • Alexandrescu S; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.
  • Wu CJ; Institute for Protein Innovation, Boston, MA, USA.
  • Keskin DB; Department of Molecular, Cell and Cancer Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • George RE; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Feng H; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Sci Adv ; 10(11): eadh9547, 2024 Mar 15.
Article in En | MEDLINE | ID: mdl-38489372
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chemokines / MARVEL Domain-Containing Proteins / N-Myc Proto-Oncogene Protein / Neuroblastoma Limits: Humans Language: En Journal: Sci Adv Year: 2024 Document type: Article Affiliation country: United States Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chemokines / MARVEL Domain-Containing Proteins / N-Myc Proto-Oncogene Protein / Neuroblastoma Limits: Humans Language: En Journal: Sci Adv Year: 2024 Document type: Article Affiliation country: United States Country of publication: United States