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Docetaxel promotes the generation of anti-tumorigenic human macrophages

Millrud, Camilla Rydberg LU ; Mehmeti, Meliha LU and Leandersson, Karin LU (2017) In Experimental Cell Research
Abstract

The taxanes Docetaxel and Paclitaxel are two of the standard chemotherapies for patients with metastatic breast cancer. The functional effect of Docetaxel and Paclitaxel on human innate immune cells of the myeloid lineage is not well established, nor is the effects these agents have on differentiation of monocytes into macrophages and dendritic cells. Therefore, the aim with this project was to determine the effects of Docetaxel and Paclitaxel on primary human monocyte differentiation, activation and function. For this purpose, primary human monocytes were isolated from healthy donors and cultured with or without Docetaxel and Paclitaxel. We found that Docetaxel promoted the differentiation of primary human monocytes into... (More)

The taxanes Docetaxel and Paclitaxel are two of the standard chemotherapies for patients with metastatic breast cancer. The functional effect of Docetaxel and Paclitaxel on human innate immune cells of the myeloid lineage is not well established, nor is the effects these agents have on differentiation of monocytes into macrophages and dendritic cells. Therefore, the aim with this project was to determine the effects of Docetaxel and Paclitaxel on primary human monocyte differentiation, activation and function. For this purpose, primary human monocytes were isolated from healthy donors and cultured with or without Docetaxel and Paclitaxel. We found that Docetaxel promoted the differentiation of primary human monocytes into pro-inflammatory macrophages with an M1 phenotype and an ability to present antigens to T cells. Monocytes treated with Docetaxel also displayed an elevated secretion of IL-8 and IL-1β, but did not promote generation of monocytic myeloid-derived suppressor cells. In conclusion, Docetaxel appears to have an immune stimulatory effect that would be beneficial for an anti-tumorigenic type of immune response, whereas Paclitaxel seems to have less effect on myeloid cells.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Activation, Docetaxel, M1 macrophages, MDSCs, Paclitaxel
in
Experimental Cell Research
publisher
Academic Press
external identifiers
  • scopus:85038822123
ISSN
0014-4827
DOI
10.1016/j.yexcr.2017.12.018
language
English
LU publication?
yes
id
d187642b-d630-4215-b09e-4c3f988160f3
date added to LUP
2018-01-04 13:22:33
date last changed
2018-01-05 03:00:03
@article{d187642b-d630-4215-b09e-4c3f988160f3,
  abstract     = {<p>The taxanes Docetaxel and Paclitaxel are two of the standard chemotherapies for patients with metastatic breast cancer. The functional effect of Docetaxel and Paclitaxel on human innate immune cells of the myeloid lineage is not well established, nor is the effects these agents have on differentiation of monocytes into macrophages and dendritic cells. Therefore, the aim with this project was to determine the effects of Docetaxel and Paclitaxel on primary human monocyte differentiation, activation and function. For this purpose, primary human monocytes were isolated from healthy donors and cultured with or without Docetaxel and Paclitaxel. We found that Docetaxel promoted the differentiation of primary human monocytes into pro-inflammatory macrophages with an M1 phenotype and an ability to present antigens to T cells. Monocytes treated with Docetaxel also displayed an elevated secretion of IL-8 and IL-1β, but did not promote generation of monocytic myeloid-derived suppressor cells. In conclusion, Docetaxel appears to have an immune stimulatory effect that would be beneficial for an anti-tumorigenic type of immune response, whereas Paclitaxel seems to have less effect on myeloid cells.</p>},
  author       = {Millrud, Camilla Rydberg and Mehmeti, Meliha and Leandersson, Karin},
  issn         = {0014-4827},
  keyword      = {Activation,Docetaxel,M1 macrophages,MDSCs,Paclitaxel},
  language     = {eng},
  month        = {12},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {Docetaxel promotes the generation of anti-tumorigenic human macrophages},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2017.12.018},
  year         = {2017},
}