Avid Bioservices Inc (CDMO)

[hutschi]

Resolving the dark side of therapy-driven cancer cell death

Published December 20, 2017

Further experiments in the study support a model in which exposure of phosphatidylserine by dead cells leads to macrophage-dependent inflammatory cytokine production that fuels tumor growth. Accordingly, the tumor-promoting role of cancer cell debris was impaired in the absence of macrophages or after the blockade of phosphatidylserine. Remarkably, antibody-mediated blockade of the individual inflammatory cytokines and chemokines TNF, IL-6, CCL4, and CCL5 each diminished the dead cell–driven tumor growth enhancement. Moreover, combined blockade of all these four factors fully abrogated the cancer­-enhancing features of dead cells. These findings put forward the hypothesis that neutralization of many inflammatory mediators and/or the use of broad-spectrum anti-inflammatory drugs might limit the detrimental effects of therapy-induced cell death and tip the balance toward suppression of tumor growth (see figure).

http://jem.rupress.org/content/early/2017/12/19/jem.20172044