TY - JOUR T1 - Neuroblastoma formation requires unconventional CD4 T cells and myeloid amino acid metabolism JF - bioRxiv DO - 10.1101/2021.02.08.430292 SP - 2021.02.08.430292 AU - Lee-Ann Van de Velde AU - E. Kaitlynn Allen AU - Jeremy Chase Crawford AU - Taylor L. Wilson AU - Clifford S. Guy AU - Marion Russier AU - Leonie Zeitler AU - Armita Bahrami AU - David Finkelstein AU - Stephane Pelletier AU - Stacey Schultz-Cherry AU - Paul G. Thomas AU - Peter J. Murray Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/02/08/2021.02.08.430292.abstract N2 - By mirroring their function as tissue repair organizers in normal tissues, immune cells regulate tumor growth. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunological manipulation with non-invasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Using spatial transcriptomic analysis, we co-localized CD4+ and myeloid populations 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+, or NK cells, prevented tumor formation. Tumor CD4+ T cells displayed unconventional phenotypes, were clonotypically diverse, and antigen-independent. Within the myeloid fraction, tumor growth required myeloid cells expressing Arginase-1. Overall, our results suggest that arginine-metabolizing myeloid cells conspire with pathogenic CD4+ T cells to create permissive conditions for tumor formation, and therefore suggest that these pro-tumorigenic pathways can be disabled by targeting myeloid amino acid metabolism.Competing Interest StatementThe authors have declared no competing interest. ER -