Journal of Clinical and Cellular Immunology
Open Access

Loss of TLR4 prevents tumor progression through metabolic reprogramming of tumor-associated macrophages

Conference Series LLC Joint International Event on 5^th European Immunology & Innate Immunity

July 21-23, 2016 Berlin, Germany

Liyun Shi, Yina Ding, Zhe Lu, Bing Wang and Songxue Wang

Hangzhou Normal University, China
Nanjing University of Chinese Medicine, China

Posters & Accepted Abstracts: J Clin Cell Immunol

Abstract :

The differentiation of macrophages with diverse effector functions is accompanied by changes in metabolism. Till now we know little about how macrophages sense and translate the environment cues into the metabolic signaling to reprogram their functional phenotypes. Here, we show that toll-like receptor 4 (TLR4) expressions in tumor associated macrophages (TAMs) was up-regulated during cancer development and inversely with tumor progression. Genetic abrogation of TLR4 in mice inhibited lung cancer development and the in vivo depletion of macrophages showed that these cells were essential for the anti-tumoral responses. We show that the activation of TLR4 in macrophages resulted in Akt/MTOR activation, Bcl6-mediated inhibition of glycolysis and therefore tumor-promoting M2-state. In contrast, deletion of TLR4 enabled macrophages to transform to Hif-1�?�?�?± driven glycolysis and the resultant tumor inhibiting M1 state. Moreover, our study demonstrates that TLR4 mediated macrophage polarization significantly impacted tumor progression and stemness like traits. This study reveals that the TLR signaling in TAMs may constitute a metabolic barrier for immunological elimination of tumors and hence a potential target for immunotherapy for cancers.