Cancer cell-intrinsic STING is associated with CD8 + T-cell infiltration and might serve as a potential immunotherapeutic target in hepatocellular ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2021-01-27

AUTHORS

Y. Zhang, Q. Zhai, X. Feng, D. Chen, Y. Lu, J. Hu, H. Xie, L. Zhou, J. Wu, S. Zheng

ABSTRACT

PurposeThe activation of stimulator of interferon genes (STING) pathway triggers the antitumor immunity by CD8 + T cells. However, the differentiated antitumor effects of STING activation in different cell types is still unclear. We aimed to investigate the expression and potential prognostic value of cancer cell-intrinsic STING in hepatocellular carcinoma (HCC), and whether STING could be a potential immunotherapeutic target of HCC was then evaluated.MethodsWe separately assessed the expression of STING in cancer cells and infiltrating immune cells in HCC tissues. The independent clinicopathological factors associated with survival outcomes were evaluated by the multivariable analysis. The HCC orthotopic mice model were used to confirm the immunotherapeutic effects of STING agonists, and CD8 + T-cell infiltration level was analyzed through immunofluorescence and flow cytometry.ResultsThe expression of cancer cell-intrinsic STING was significantly reduced in HCC compared with adjacent tissues. Patients with low levels of cancer cell-intrinsic STING expression was associated with increased tumor volume (P = 0.009), higher serum AFP levels (P = 0.028), and decreased CD8 + T-cell infiltration (P = 0.002). Low levels of cancer cell-intrinsic STING expression indicated a poor overall survival (OS) and disease-free survival (DFS). Multivariate analysis demonstrated that low levels of cancer cell-intrinsic STING expression was an independent prognostic factor. Additionally, cancer cell-intrinsic STING expression was positively related with CD8 + T-cell infiltration levels in HCC patients (r = 0.308; P = 0.001). When mice with orthotopic HCC tumors treated with STING agonists, tumor growth was significantly reduced with enhanced levels of CD8 + T-cell infiltration.ConclusionCancer cell-intrinsic STING might affect HCC tumor progression through enhancing CD8 + T-cell infiltration and can be an immunotherapeutic target for HCC. More... »

PAGES

1314-1324

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12094-020-02519-z

DOI

http://dx.doi.org/10.1007/s12094-020-02519-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1134930420

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33502741


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25 schema:description PurposeThe activation of stimulator of interferon genes (STING) pathway triggers the antitumor immunity by CD8 + T cells. However, the differentiated antitumor effects of STING activation in different cell types is still unclear. We aimed to investigate the expression and potential prognostic value of cancer cell-intrinsic STING in hepatocellular carcinoma (HCC), and whether STING could be a potential immunotherapeutic target of HCC was then evaluated.MethodsWe separately assessed the expression of STING in cancer cells and infiltrating immune cells in HCC tissues. The independent clinicopathological factors associated with survival outcomes were evaluated by the multivariable analysis. The HCC orthotopic mice model were used to confirm the immunotherapeutic effects of STING agonists, and CD8 + T-cell infiltration level was analyzed through immunofluorescence and flow cytometry.ResultsThe expression of cancer cell-intrinsic STING was significantly reduced in HCC compared with adjacent tissues. Patients with low levels of cancer cell-intrinsic STING expression was associated with increased tumor volume (P = 0.009), higher serum AFP levels (P = 0.028), and decreased CD8 + T-cell infiltration (P = 0.002). Low levels of cancer cell-intrinsic STING expression indicated a poor overall survival (OS) and disease-free survival (DFS). Multivariate analysis demonstrated that low levels of cancer cell-intrinsic STING expression was an independent prognostic factor. Additionally, cancer cell-intrinsic STING expression was positively related with CD8 + T-cell infiltration levels in HCC patients (r = 0.308; P = 0.001). When mice with orthotopic HCC tumors treated with STING agonists, tumor growth was significantly reduced with enhanced levels of CD8 + T-cell infiltration.ConclusionCancer cell-intrinsic STING might affect HCC tumor progression through enhancing CD8 + T-cell infiltration and can be an immunotherapeutic target for HCC.
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31 schema:keywords AFP levels
32 CD8
33 HCC patients
34 HCC tissues
35 HCC tumor progression
36 HCC tumors
37 MethodsWe
38 STING activation
39 STING agonists
40 STING expression
41 T cell infiltration
42 T cell infiltration levels
43 T cells
44 activation
45 adjacent tissues
46 agonists
47 analysis
48 antitumor effects
49 antitumor immunity
50 cancer cells
51 carcinoma
52 cell types
53 cells
54 clinicopathological factors
55 cytometry
56 different cell types
57 disease-free survival
58 effect
59 enhanced levels
60 expression
61 expression of STING
62 factors
63 gene pathways
64 growth
65 hepatocellular carcinoma
66 high serum AFP level
67 immune cells
68 immunity
69 immunofluorescence
70 immunotherapeutic effects
71 immunotherapeutic target
72 independent clinicopathological factors
73 independent prognostic factor
74 infiltration
75 infiltration levels
76 interferon genes (STING) pathway
77 levels
78 low levels
79 mice
80 model
81 mouse model
82 multivariable analysis
83 multivariate analysis
84 orthotopic HCC tumors
85 outcomes
86 overall survival
87 pathway
88 patients
89 poor overall survival
90 potential immunotherapeutic target
91 potential prognostic value
92 prognostic factors
93 prognostic value
94 progression
95 serum AFP level
96 stimulator
97 stings
98 survival
99 survival outcomes
100 target
101 tissue
102 tumor growth
103 tumor progression
104 tumor volume
105 tumors
106 types
107 values
108 volume
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