| First Author | Van de Velde LA | Year | 2021 |
| Journal | Cancer Res | Volume | 81 |
| Issue | 19 | Pages | 5047-5059 |
| PubMed ID | 34301764 | Mgi Jnum | J:310828 |
| Mgi Id | MGI:6764430 | Doi | 10.1158/0008-5472.CAN-21-0691 |
| Citation | Van de Velde LA, et al. (2021) Neuroblastoma formation requires unconventional CD4 T cells and Arginase-1-dependent myeloid cells. Cancer Res |
| abstractText | 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 immunological manipulation with non-invasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Spatial transcriptomic analysis showed that CD4+ and myeloid populations co-localized 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 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 pro-tumorigenic pathways could be disabled by targeting myeloid arginine metabolism. |
