Format

Send to

Choose Destination
See comment in PubMed Commons below
Semin Immunol. 2014 Feb;26(1):38-47. doi: 10.1016/j.smim.2014.01.008. Epub 2014 Mar 3.

The two faces of IL-6 in the tumor microenvironment.

Author information

1
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, United States.
2
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, United States. Electronic address: sharon.evans@roswellpark.org.

Abstract

Within the tumor microenvironment, IL-6 signaling is generally considered a malevolent player, assuming a dark visage that promotes tumor progression. Chronic IL-6 signaling is linked to tumorigenesis in numerous mouse models as well as in human disease. IL-6 acts intrinsically on tumor cells through numerous downstream mediators to support cancer cell proliferation, survival, and metastatic dissemination. Moreover, IL-6 can act extrinsically on other cells within the complex tumor microenvironment to sustain a pro-tumor milieu by supporting angiogenesis and tumor evasion of immune surveillance. A lesser known role for IL-6 signaling has recently emerged in which it plays a beneficial role, presenting a fairer face that opposes tumor growth by mobilizing anti-tumor T cell immune responses to attain tumor control. Accumulating evidence establishes IL-6 as a key player in the activation, proliferation and survival of lymphocytes during active immune responses. IL-6 signaling can also resculpt the T cell immune response, shifting it from a suppressive to a responsive state that can effectively act against tumors. Finally, IL-6 plays an indispensable role in boosting T cell trafficking to lymph nodes and to tumor sites, where they have the opportunity to become activated and execute their cytotoxic effector functions, respectively. Here, we discuss the dual faces of IL-6 signaling in the tumor microenvironment; the dark face that drives malignancy, and the fairer aspect that promotes anti-tumor adaptive immunity.

KEYWORDS:

Adaptive tumor immunity; IL-6 trans-signaling; T cell trafficking; Tumorigenesis

PMID:
24602448
PMCID:
PMC3970580
DOI:
10.1016/j.smim.2014.01.008
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center