Thursday, August 23, 2012 7:44:15 PM
and bavituximab which could explain a bigger effect in the second-line trial.
It would be a lot easier to figure out if the first-line trial also used docetaxel.
This paper explored the immunomodulatory aspects of docetaxel.
A Novel Chemoimmunomodulating Property of Docetaxel:
Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers
Krithika N. Kodumudi, Karrune Woan, Danielle L. Gilvary, et al.
FREE: http://clincancerres.aacrjournals.org/content/16/18/4583.full.pdf+html
From the Discussion
....
These studies show the novel finding that docetaxel
directly modulates MDSC signaling and therefore phenotype
and function (i.e., cytokine) in vitro. Moreover, as
evidenced by the MDSC splenic leukocyte coculture,
MDSCs may be able to influence polarization of T cells
as well. The in vivo circumstances may be more complex,
but it can be inferred that docetaxel can directly induce an
M1-like polarization of MDSCs and contribute to an overall
shift toward M1/Th1 antitumor responses. However, it
does not rule out the possibility of paracrine contribution
of T cells and other leukocytes. Until now, in vivo docetaxel
treatment is thought to reduce tumor burden through direct
cytotoxicity (41); however, in this study, we show an
indirect immunomodulatory mechanism as well. As previously
mentioned, MDSC accumulation has been correlated
directly with tumor burden (8). Thus, there may be
synergism between multiple mechanisms of action of docetaxel
(i.e., direct cytotoxicity to tumors and a specific
subset of MDSCs and indirect antitumor responses via
immunomodulation).
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