Sorafenib induces autophagy and suppresses activation of human macrophage

Abstract

Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.

Autophagy-mediated regulation of macrophages and its applications for cancer

“…71 Interestingly, recent studies showed that sorafenib exerts a potent effect on macrophages by inducing autophagy and suppressing the expression of CD80, a marker of the M1 phenotype, suggesting the possible correlation between autophagy and macrophage polarization and highlighting the protumorigenic effect of sorafenib through modulation of macrophage polarization by autophagy. 72 Altogether, these findings support a key role of autophagy in the regulation of macrophage polarization in the tumor microenvironment (Fig. 3).…”

“…16 Several studies have shown that treatments targeting autophagy can modify the activation states of macrophages. 62,63,66,67,72 These findings should encourage studies to develop genetic and pharmacological approaches to skew TAM polarization to the M1 phenotype by targeting autophagy. For example, even if TLR2 deficiency causes a reduction of macrophage infiltration, this ablation also induces a significant suppression of autophagy and a reduction in the expression of TNF/ TNFα (tumor necrosis factor), IFNG (interferon, gamma) and CXCL2 (chemokine [C-X-C motif] ligand 2) in liver tissues, indicating an increase of M2 macrophage polarization, which in turn promotes hepatocarcinogenesis.…”

Interleukin-6 as an emerging regulator of renal cell cancer

“…Sunitinib has recently been shown to elicit its antitumor activity by STAT3 inhibition, indicating consolidation of IL-6 activity as a molecule that triggers RCC development [60]. This is in contradiction to sorafenib, which does not reduce macrophage secretion of protumorigenic IL-6 [90]. As there are no molecular studies about molecular correlation or effect between IL-6 signaling pathways and sorafenib or sunitinib, we hypothesize that the observed differences may be due to different molecular targets for these 2 inhibitors.…”

Immunotherapy advances in uro-genital malignancies

“…Next to their antiangiogenic activity, TKIs may also exert an immunomodulatory effect (sorafenib seems to have immunosuppressive actions and can induce autophagy and activation of tumor-associated macrophages; sunitinib seems to stimulate immune response against tumor by decreasing the efficacy of suppressor cells which are involved in angiogenesis in RCC) (Porta et al, 2011;Lin et al, 2013;Ko et al, 2010;Ning et al, 2012). This has prepared the groundwork for combinations of new generation immunotherapies with standard treatment in RCC, in order to evaluate safety profile and efficacy.…”