T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.

Details

Serval ID
serval:BIB_FE6933D4F057
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.
Journal
Science translational medicine
Author(s)
Neubert N.J., Schmittnaegel M., Bordry N., Nassiri S., Wald N., Martignier C., Tillé L., Homicsko K., Damsky W., Maby-El Hajjami H., Klaman I., Danenberg E., Ioannidou K., Kandalaft L., Coukos G., Hoves S., Ries C.H., Fuertes Marraco S.A., Foukas P.G., De Palma M., Speiser D.E.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
11/04/2018
Peer-reviewed
Oui
Volume
10
Number
436
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage differentiation that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and patients with metastatic melanoma have increased CSF1 in blood compared to healthy subjects. In tumors, CSF1 expression correlated with the abundance of CD8 <sup>+</sup> T cells and CD163 <sup>+</sup> TAMs. Human melanoma cell lines consistently produced CSF1 after exposure to melanoma-specific CD8 <sup>+</sup> T cells or T cell-derived cytokines in vitro, reflecting a broadly conserved mechanism of CSF1 induction by activated CD8 <sup>+</sup> T cells. Mining of publicly available transcriptomic data sets suggested co-enrichment of CD8 <sup>+</sup> T cells with CSF1 or various TAM-specific markers in human melanoma, which was associated with nonresponsiveness to programmed cell death protein 1 (PD1) checkpoint blockade in a smaller patient cohort. Combination of anti-PD1 and anti-CSF1 receptor (CSF1R) antibodies induced the regression of BRAF <sup>
V600E
</sup> -driven, transplant mouse melanomas, a result that was dependent on the effective elimination of TAMs. Collectively, these data implicate CSF1 induction as a CD8 <sup>+</sup> T cell-dependent adaptive resistance mechanism and show that simultaneous CSF1R targeting may be beneficial in melanomas refractory to immune checkpoint blockade and, possibly, other T cell-based therapies.
Keywords
Animals, Antigens, CD/metabolism, Antigens, Differentiation, Myelomonocytic/metabolism, CD8-Positive T-Lymphocytes/metabolism, Cell Differentiation/physiology, Cell Line, Tumor, Humans, Macrophage Colony-Stimulating Factor/blood, Macrophages/metabolism, Melanoma/blood, Melanoma/pathology, Mice, Proto-Oncogene Proteins B-raf/metabolism, Receptors, Cell Surface/metabolism, Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
19/04/2018 21:17
Last modification date
27/09/2019 11:32
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