Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2005 Dec;11(12):1314-21.
doi: 10.1038/nm1325. Epub 2005 Nov 20.

Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity

Marcin Kortylewski  1 , Maciej Kujawski, Tianhong Wang, Sheng Wei, Shumin Zhang, Shari Pilon-Thomas, Guilian Niu, Heidi Kay, James Mulé, William G Kerr, Richard Jove, Drew Pardoll, Hua Yu
Affiliations
Comparative Study

Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity

Marcin Kortylewski et al. Nat Med. 2005 Dec.

Abstract

The immune system can act as an extrinsic suppressor of tumors. Therefore, tumor progression depends in part on mechanisms that downmodulate intrinsic immune surveillance. Identifying these inhibitory pathways may provide promising targets to enhance antitumor immunity. Here, we show that Stat3 is constitutively activated in diverse tumor-infiltrating immune cells, and ablating Stat3 in hematopoietic cells triggers an intrinsic immune-surveillance system that inhibits tumor growth and metastasis. We observed a markedly enhanced function of dendritic cells, T cells, natural killer (NK) cells and neutrophils in tumor-bearing mice with Stat3(-/-) hematopoietic cells, and showed that tumor regression requires immune cells. Targeting Stat3 with a small-molecule drug induces T cell- and NK cell-dependent growth inhibition of established tumors otherwise resistant to direct killing by the inhibitor. Our findings show that Stat3 signaling restrains natural tumor immune surveillance and that inhibiting hematopoietic Stat3 in tumor-bearing hosts elicits multicomponent therapeutic antitumor immunity.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources