CKLF instigates a “cold” microenvironment to promote MYCN-mediated tumor aggressiveness-Reference-Cited by-同舟云学术

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

Published:2024-03-15 Issue:11 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Qin Xiaodan¹^ORCID,Lam Andrew¹^ORCID,Zhang Xu¹²^ORCID,Sengupta Satyaki³,Iorgulescu J. Bryan⁴⁵^ORCID,Ni Hongru¹,Das Sanjukta³⁶^ORCID,Rager Madison¹^ORCID,Zhou Zhenwei⁷^ORCID,Zuo Tao⁸^ORCID,Meara Grace K.¹,Floru Alexander E.¹^ORCID,Kemet Chinyere¹^ORCID,Veerapaneni Divya¹^ORCID,Kashy Daniel¹^ORCID,Lin Liang⁴,Lloyd Kenneth⁹^ORCID,Kwok Lauren¹^ORCID,Smith Kaylee S.¹,Nagaraju Raghavendar T.¹⁰¹¹^ORCID,Meijers Rob⁹,Ceol Craig¹²^ORCID,Liu Ching-Ti⁷^ORCID,Alexandrescu Sanda¹³,Wu Catherine J.⁴¹⁴^ORCID,Keskin Derin B.⁴¹⁵¹⁶¹⁷¹⁸^ORCID,George Rani E.³,Feng Hui¹^ORCID

Affiliation:

1. 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.

2. Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, China.

3. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

4. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

5. Molecular Diagnostics Laboratory, Department of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

6. School of Biotechnology, KIIT University, Bhubanesw, India.

7. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

8. Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, MA, USA.

9. Institute for Protein Innovation, Boston, MA, USA.

10. Faculty of Biology, Medicine and Health, Division of Cancer Sciences, University of Manchester, Manchester, UK.

11. Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.

12. Department of Molecular, Cell and Cancer Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.

13. Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA.

14. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

15. Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

16. Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.

17. Department of Computer Science, Metropolitan College, Boston University, Boston, MA, USA.

18. Broad Institute of MIT and Harvard, Cambridge, MA, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adh9547

Reference82 articles.

1. The Expanding World of N-MYC–Driven Tumors

2. Molecular Mechanisms of MYCN Dysregulation in Cancers

3. Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions

4. Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression

5. Clinically Relevant Cytotoxic Immune Cell Signatures and Clonal Expansion of T-Cell Receptors in High-Risk MYCN-Not-Amplified Human Neuroblastoma

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