La Trobe
1188782_Allam,A_2021.pdf (2.54 MB)
Download file

Exploiting the STAT3 Nexus in Cancer-Associated Fibroblasts to Improve Cancer Therapy

Download (2.54 MB)
journal contribution
posted on 05.01.2022, 23:57 authored by Amr AllamAmr Allam, Marina Yakou, Lok Man PangLok Man Pang, Matthias ErnstMatthias Ernst, Jennifer HuynhJennifer Huynh
The tumor microenvironment (TME) is composed of a heterogenous population of cells that exist alongside the extracellular matrix and soluble components. These components can shape an environment that is conducive to tumor growth and metastatic spread. It is well-established that stromal cancer-associated fibroblasts (CAFs) in the TME play a pivotal role in creating and maintaining a growth-permissive environment for tumor cells. A growing body of work has uncovered that tumor cells recruit and educate CAFs to remodel the TME, however, the mechanisms by which this occurs remain incompletely understood. Recent studies suggest that the signal transducer and activator of transcription 3 (STAT3) is a key transcription factor that regulates the function of CAFs, and their crosstalk with tumor and immune cells within the TME. CAF-intrinsic STAT3 activity within the TME correlates with tumor progression, immune suppression and eventually the establishment of metastases. In this review, we will focus on the roles of STAT3 in regulating CAF function and their crosstalk with other cells constituting the TME and discuss the utility of targeting STAT3 within the TME for therapeutic benefit.

Funding

Funding M. Ernst is a recipient of Investigator and Program Grant support from the National Health and Medical Research Council (NHMRC) Australia (1173814).

History

Publication Date

11/11/2021

Journal

Frontiers in Immunology

Volume

12

Article Number

767939

Pagination

14p.

Publisher

Frontiers Media S.A.

ISSN

1664-3224

Rights Statement

© 2021 Allam, Yakou, Pang, Ernst and Huynh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.