Van de Velde, Lee-AnnAllen, E. KaitlynnCrawford, Jeremy ChaseWilson, Taylor L.Guy, Clifford S.Russier, MarionZeitler, LeonieBahrami, ArmitaFinkelstein, DavidPelletier, StephaneSchultz-Cherry, StaceyThomas, Paul G.Murray, Peter J.2024-09-302024-09-302021Van de Velde LA, Allen EK, Crawford JC, et al. Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells. Cancer Res. 2021;81(19):5047-5059. doi:10.1158/0008-5472.CAN-21-0691https://hdl.handle.net/1805/43666Immune 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.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalNeuroblastomaArginaseDisease susceptibilityTranscriptomeArticle