BackgroundThe M2 phenotype of tumor-associated macrophages (TAM) inhibits the anti-tumor inflammation, increases angiogenesis and promotes tumor progression. The transcription factor Nuclear Factor (erythroid-derived 2)-Like 2 (Nrf2) not only modulates the angiogenesis but also plays the anti-inflammatory role through inhibiting pro-inflammatory cytokines expression; however, the role of Nrf2 in the cancer cell and macrophages interaction is not clear.MethodsHepatocellular carcinoma cells (Hep G2 and Huh 7) and pancreatic cancer cells (SUIT2 and Panc-1) were co-cultured with monocytes cells (THP-1) or peripheral blood monocytes derived macrophages, then the phenotype changes of macrophages and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of Nrf2 in cancer cells and macrophages interaction were investigated.ResultsIn this study, we found that cancer cells could induce an M2-like macrophage characterized by up-regulation of CD163 and Arg1, and down-regulation of IL-1b and IL-6 through Nrf2 activation. Also, Nrf2 activation of macrophages promoted VEGF expression. The Nrf2 activation of macrophages correlated with the reactive oxygen species induced by cancer cells derived lactate. Cancer cells educated macrophages could activate Nrf2 of the cancer cells, in turn, to increase cancer cells epithelial-mesenchymal transition (EMT) through paracrine VEGF. These findings suggested that Nrf2 played the important role in the cancer cells and macrophages interaction.ConclusionsMacrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM interaction and suggests a potential therapeutic target.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0262-x) contains supplementary material, which is available to authorized users.

Targeting the tumor stroma is an important strategy in cancer treatment. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor-1 (PAI-1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI-1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells in vitro. It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL-6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI-1 expression was upregulated in TAMs after being stimulated with CAF-conditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelial-mesenchymal transition. CAFs were the main producer of C-X-C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI-1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI-1 secretion via CXCL12. Furthermore, it was found that PAI-1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.

Objective: The aim of this study was to investigate the potential of an intraoperative 3D hologram, which was a computer graphics model liver, with mixed reality techniques in liver surgery. Summary Background Data: The merits for the application of a hologram for surgical support are: 1) no sterilized display monitor; 2) better spatial awareness; and 3) 3D images shared by all the surgeons. Methods: 3D polygon data using preoperative computed tomography data was installed into head mount displays, HoloLens (Microsoft Corporation, Redmond, WA). Results: In a Wi-Fi-enabled operative room, several surgeons wearing HoloLens succeeded in sharing the same hologram and moving that hologram from respective operators’ angles by means of easy gesture-handling without any monitors. The intraoperative hologram contributed to better imagination of tumor locations, and for determining the parenchymal dissection line in the hepatectomy for the patients with more than 20 multiple colo-rectal liver metastases. In another case, the hologram enabled a safe Gliisonean pedicle approach for hepato-cellular carcinoma with a hilar anatomical anomaly. Surgeons could easily compare the real patient's anatomy and that of the hologram just before the hepatic hilar procedure. Conclusions: This initial experience suggested that an intraoperative hologram with mixed reality techniques contributed to “last-minute simulation,” not for “navigation.” The intraoperative hologram might be a new next-generation operation-supportive tool in terms of spatial awareness, sharing, and simplicity.

These results revealed that impaired liver regeneration was due to aging, which was expressed by decreased cell cycle and increased autophagy and apoptosis. Therefore, understanding the molecular basis for aged liver regeneration might provide a new therapeutic option for old patients.

Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.