Background
Changes in glycogen metabolism is an essential feature among the various metabolic adaptations used by cancer cells to adjust to the conditions imposed by the tumor microenvironment. Our previous study showed that glycogen branching enzyme (GBE1) is downstream of the HIF1 pathway in hypoxia-conditioned lung cancer cells. In the present study, we investigated whether GBE1 is involved in the immune regulation of the tumor microenvironment in lung adenocarcinoma (LUAD).
Methods
We used RNA-sequencing analysis and the multiplex assay to determine changes in GBE1 knockdown cells. The role of GBE1 in LUAD was evaluated both in vitro and in vivo.
Results
GBE1 knockdown increased the expression of chemokines CCL5 and CXCL10 in A549 cells. CD8 expression correlated positively with CCL5 and CXCL10 expression in LUAD. The supernatants from the GBE1 knockdown cells increased recruitment of CD8
+
T lymphocytes. However, the neutralizing antibodies of CCL5 or CXCL10 significantly inhibited cell migration induced by shGBE1 cell supernatants. STING/IFN-I pathway mediated the effect of GBE1 knockdown for CCL5 and CXCL10 upregulation. Moreover, PD-L1 increased significantly in shGBE1 A549 cells compared to those in control cells. Additionally, in LUAD tumor tissues, a negative link between PD-L1 and GBE1 was observed. Lastly, blockade of GBE1 signaling combined with anti-PD-L1 antibody significantly inhibited tumor growth in vivo.
Conclusions
GBE1 blockade promotes the secretion of CCL5 and CXCL10 to recruit CD8
+
T lymphocytes to the tumor microenvironment via the IFN-I/STING signaling pathway, accompanied by upregulation of PD-L1 in LUAD cells, suggesting that GBE1 could be a promising target for achieving tumor regression through cancer immunotherapy in LUAD.
Electronic supplementary material
The online version of this article (10.1186/s12943-019-1027-x) contains supplementary material, which is available to authorized users.
The self-absorption effect seriously affects the accuracy of determination in laser-induced breakdown spectroscopy (LIBS). In this work, we proposed to reduce multielemental self-absorption within a wide spectral range (200-900 nm) by using microwave-assisted excitation in LIBS (MAE-LIBS). Self-absorption reduction of sodium (Na), potassium (K), aluminum (Al), silicon (Si), and calcium (Ca) in potassium feldspar using MAE-LIBS was investigated. The mechanisms of self-absorption reduction in MAE-LIBS were also investigated. The results show that the serious self-absorption of spectral lines (Na and K) was reduced. The full widths at half maximum (FWHMs) of Na I 589.0 nm, Na I 589.6 nm, K I 766.5 nm, and K I 769.9 nm in potassium feldspar were reduced by 43%, 43%, 53%, and 47%, respectively. MAE-LIBS also has a little FWHM reduction for spectral lines with weak self-absorption. The results demonstrate that MAE-LIBS can simultaneously reduce multielemental self-absorption.
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