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  Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells

Van de Velde, L.-A., Allen, E. K., Crawford, J. C., Wilson, T. L., Guy, C. S., Russier, M., et al. (2021). Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells. Cancer Research, 81(19), 5047-5059. doi:10.1158/0008-5472.CAN-21-0691.

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 Creators:
Van de Velde, Lee-Ann1, Author
Allen, E. Kaitlynn1, Author
Crawford, Jeremy Chase1, Author
Wilson, Taylor L.1, Author
Guy, Clifford S.1, Author
Russier, Marion2, Author           
Zeitler, Leonie2, Author           
Bahrami, Armita1, Author
Finkelstein, David1, Author
Pelletier, Stephane1, Author
Schultz-Cherry, Stacey1, Author
Thomas, Paul G.1, Author
Murray, Peter J.2, Author           
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1external, ou_persistent22              
2Murray, Peter / Immunoregulation, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466696              

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Free keywords: INFECTIOUS TOLERANCE; IMMUNE CELLS; B-CELLS; TUMOR; EXPRESSION; CANCER; RECEPTOR; MACROPHAGES; MYCN; INFLAMMATIONOncology;
 Abstract: Immune cells regulate tumor growth by mirroring their function as tissue repair organizers in normal tissues. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunologic manipulation with noninvasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Spatial transcriptomic analysis showed that CD4(+) and myeloid populations colocalized within the tumor parenchyma, while CD8(+) T cells and B cells were peripherally dispersed. Depletion of CD4(+) T cells or CCR2(+) macrophages, but not B cells, CD8(+) T cells, or natural killer (NK) cells, prevented tumor formation. Tumor CD4(+) T cells displayed unconventional phenotypes and were clonotypically diverse and antigen independent. Within the myeloid fraction, tumor growth required myeloid cells expressing arginase-1. Overall, these results demonstrate how arginine-metabolizing myeloid cells conspire with pathogenic CD4(+) T cells to create permissive conditions for tumor formation, suggesting that these protumorigenic pathways could be disabled by targeting myeloid arginine metabolism.
Significance: A new model of human neuroblastoma provides ways to track tumor formation and expansion in living animals, allowing identification of CD4(+) T-cell and macrophage functions required for oncogenesis.
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Language(s): eng - English
 Dates: 2021
 Publication Status: Issued
 Pages: 13
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Title: Cancer Research
Source Genre: Journal
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Publ. Info: Baltimore, Md. : Waverly Press
Pages: - Volume / Issue: 81 (19) Sequence Number: - Start / End Page: 5047 - 5059 Identifier: ISSN: 0008-5472
CoNE: https://pure.mpg.de/cone/journals/resource/991042743115962_1