Tumor-Associated Macrophages Suppress the Cytotoxic Activity of Antimitotic Agents

• DOI: 10.1016/j.celrep.2017.03.038
• Publication Date: 2017-04-04T17:38:18Z
• Authors: Oakley C. Olson; Hyunjung Kim; Daniela F. Quail; Emily A. Foley; Johanna A. Joyce
• Keywords: Mitotic catastrophe

Antimitotic agents, including Taxol, disrupt microtubule dynamics and cause a protracted mitotic arrest subsequent cell death. Despite the broad utility of these drugs in breast cancer other tumor types, clinical response remains variable. Tumor-associated macrophages (TAMs) suppress duration Taxol-induced cells promote earlier slippage. This correlates with decrease phosphorylated form histone H2AX (γH2AX), decreased p53 activation, reduced death interphase. TAMs viability following slippage manner sensitive to MAPK/ERK kinase (MEK) inhibition. Acute depletion major histocompatibility complex class II low (MHCIIlo) increased DNA damage apoptosis cells, leading greater efficacy intervention trials. MEK inhibition blocked protective capacity phenocopied effects TAM on Taxol treatment. cytotoxic part through non-autonomous modulation targeting TAM-cancer interactions potentiates efficacy.