| First Author | Nixon BG | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 11 | Pages | 2044-2058.e5 |
| PubMed ID | 36288724 | Mgi Jnum | J:331110 |
| Mgi Id | MGI:7386637 | Doi | 10.1016/j.immuni.2022.10.002 |
| Citation | Nixon BG, et al. (2022) Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer. Immunity 55(11):2044-2058.e5 |
| abstractText | Tumors are populated by antigen-presenting cells (APCs) including macrophage subsets with distinct origins and functions. Here, we examined how cancer impacts mononuclear phagocytic APCs in a murine model of breast cancer. Tumors induced the expansion of monocyte-derived tumor-associated macrophages (TAMs) and the activation of type 1 dendritic cells (DC1s), both of which expressed and required the transcription factor interferon regulatory factor-8 (IRF8). Although DC1s mediated cytotoxic T lymphocyte (CTL) priming in tumor-draining lymph nodes, TAMs promoted CTL exhaustion in the tumor, and IRF8 was required for TAMs' ability to present cancer cell antigens. TAM-specific IRF8 deletion prevented exhaustion of cancer-cell-reactive CTLs and suppressed tumor growth. Tumors from patients with immune-infiltrated renal cell carcinoma had abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. Furthermore, the TAM-IRF8 signature co-segregated with CTL exhaustion signatures across multiple cancer types. Thus, CTL exhaustion is promoted by TAMs via IRF8. |
