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Incorporation of microbiome data has recently become important for prevention, diagnosis, and treatment of colorectal cancer, and several species of bacteria were shown to be associated with carcinogenesis. However, the role of commensal fungi in colon cancer remains poorly understood. Here, we report that mice lacking the c-type lectin Dectin-3 (Dectin-3 -/- ) show increased tumorigenesis and Candida albicans burden upon chemical induction. Elevated C. albicans load triggered glycolysis in macrophages and interleukin-7 (IL-7) secretion. IL-7 induced IL-22 production in RORγt + (group 3) innate lymphoid cells (ILC3s) via aryl hydrocarbon receptor and STAT3. Consistently, IL-22 frequency in tumor tissues of colon cancer patients positively correlated with fungal burden, indicating the relevance of this regulatory axis in human disease. These results establish a C. albicans-driven crosstalk between macrophages and innate lymphoid cells in the intestine and expand our understanding on how commensal mycobiota regulate host immunity and promote tumorigenesis., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Low frequency magnetic fields (LF-MFs) can affect cell proliferation in a cell-type and intensity-dependent way. Previous study has reported the anti-tumor effect of LF-MFs in lung cancers. Our previous study also optimized the intensity and duration of LF-MFs to effectively inhibit the proliferation of lung cancer cells. However, the anti-tumor mechanism of LF-MFs remains unclear, which limit the clinical application of LF-MFs in anti-tumor therapy. Here, in a well-established Lewis Lung Cancer (LLC) mouse model, we found that LF-MFs inhibit tumor growth and induce an autophagic cell death in lung cancer. We also found that LF-MFs could up-regulate the expression level of miR-486, which was involved in LF-MFs activated cell autophagy. Furthermore, we found B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) is a direct target of miR-486. miR-486 inhibit AKT/mTOR signaling through inhibiting expression of BCAP. Moreover, a decreased expression of miR-486 and an increased expression of BCAP were found in tumor tissues of lung cancer patients. Taken together, this study proved that LF-MFs can inhibit lung cancers through miR-486 induced autophagic cell death, which suggest a clinical application of LF-MFs in cancer treatment.

Tumor hypoxia is one of the important features of lung adenocarcinoma. Chemokines might mediate the effects caused by tumor hypoxia. As confirmed in tumor tissue and serum of patients, CC chemokine 28 (CCL28) was the only hypoxia induced chemokine in lung adenocarcinoma cells. CCL28 could promote tube formation, migration and proliferation of endothelial cells. In addition, angiogenesis was promoted by CCL28 in the chick chorioallantoic membrane and matrigel implanted in dorsal back of athymic nude mice (CByJ.Cg-Foxn1(nu)/J). Tumors formed by lung adenocarcinoma cells with high expression of CCL28 grew faster and had a higher vascular density, whereas tumor formation rate of lung adenocarcinoma cells with CCL28 expression knockdown was quite low and had a lower vascular density. CCR3, receptor of CCL28, was highly expressed in vascular endothelial cells in lung adenocarcinoma when examining by immunohistochemistry. Further signaling pathways in endothelial cells, modulated by CCL28, were analyzed by Phosphorylation Antibody Array. CCL28/CCR3 signaling pathway could bypass that of VEGF/VEGFR on the levels of PI3K-Akt, p38 MAPK and PLC gamma. The effects could be neutralized by antibody against CCR3. In conclusion, CCL28, as a chemokine induced by tumor hypoxia, could promote angiogenesis in lung adenocarcinoma through targeting CCR3 on microvascular endothelial cells.