Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

IFN?-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment. Cell Nirschl, C. J., Suárez-Fariñas, M. n., Izar, B. n., Prakadan, S. n., Dannenfelser, R. n., Tirosh, I. n., Liu, Y. n., Zhu, Q. n., Devi, K. S., Carroll, S. L., Chau, D. n., Rezaee, M. n., Kim, T. G., Huang, R. n., Fuentes-Duculan, J. n., Song-Zhao, G. X., Gulati, N. n., Lowes, M. A., King, S. L., Quintana, F. J., Lee, Y. S., Krueger, J. G., Sarin, K. Y., Yoon, C. H., Garraway, L. n., Regev, A. n., Shalek, A. K., Troyanskaya, O. n., Anandasabapathy, N. n. 2017; 170 (1): 127–41.e15

Abstract

Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFN? is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFN?-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFN?. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.

View details for PubMedID 28666115