Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy.

Details

Serval ID
serval:BIB_34CE8413C2A8
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy.
Journal
Cancers
Author(s)
Verdeil G., Lawrence T., Schmitt-Verhulst A.M., Auphan-Anezin N.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
21/11/2019
Peer-reviewed
Oui
Volume
11
Number
12
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: epublish
Abstract
Oncogene-induced STAT3-activation is central to tumor progression by promoting cancer cell expression of pro-angiogenic and immunosuppressive factors. STAT3 is also activated in infiltrating immune cells including tumor-associated macrophages (TAM) amplifying immune suppression. Consequently, STAT3 is considered as a target for cancer therapy. However, its interplay with other STAT-family members or transcription factors such as NF-κB has to be considered in light of their concerted regulation of immune-related genes. Here, we discuss new attempts at re-educating immune suppressive tumor-associated macrophages towards a CD8 T cell supporting profile, with an emphasis on the role of STAT transcription factors on TAM functional programs. Recent clinical trials using JAK/STAT inhibitors highlighted the negative effects of these molecules on the maintenance and function of effector/memory T cells. Concerted regulation of STAT3 and STAT5 activation in CD8 T effector and memory cells has been shown to impact their tumor-specific responses including intra-tumor accumulation, long-term survival, cytotoxic activity and resistance toward tumor-derived immune suppression. Interestingly, as an escape mechanism, melanoma cells were reported to impede STAT5 nuclear translocation in both CD8 T cells and NK cells. Ours and others results will be discussed in the perspective of new developments in engineered T cell-based adoptive therapies to treat cancer patients.
Keywords
STAT transcription factors, adoptive T cell therapy, immune suppression, inflammation, tumor-associated macrophages
Pubmed
Open Access
Yes
Create date
05/12/2019 23:44
Last modification date
23/01/2020 7:26
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