Antigen conjugated nanoparticles reprogrammed the tumor-conditioned macrophages toward pro-immunogenic type through regulation of NADPH oxidase and p38MAPK

Cytokine
Sourav Chattopadhyay, Somenath Roy

Abstract

Tumor associated macrophages (TAMs) are pertinent to cancer cell growth in the tumor microenvironment. Indeed, TAMs differentiate from monocytes (MΦ) due to specific growth factors present in the tumor microenvironment. TAMs show mostly an M2-like phenotype is due to the absence of pro-inflammatory signals and supply fuel to tumor growth. Several attempts have been taken to switch TAMs into a pro-immunogenic type. To address context, we used a tumor microenvironment by in vitro coculturing human blood MΦ with cancer cell conditioned media (TC-MΦ). We showed that the antigen cobalt oxide nanoparticles (Ag-NPs) can reprogram TC-MΦ to pro-immunogenic type to build up an antitumor immune response. Our results demonstrate that NPs-Ag induced a marked activation of NADPH oxidase in TC-MΦ, likely through stimulation of ROS linked to activation of p38 MAPK. These activated p38 MAPK up-regulated the IFN-γ, TNF-α and initial IL-12 production, in turn, the activation of IFN-γ prolonged IL-12 production.

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