Data from SIX4 Controls Anti-PD-1 Efficacy by Regulating STING Expression Article Swipe
Beiyuan Liang
,
Evan H. Zhang
,
Zhen Ye
,
Hayden Storts
,
Jin Wei
,
Xinru Zheng
,
Hannah Hylton
,
Olivia Zaleski
,
Xuanxuan Xing
,
Wayne Miles
,
Jing J. Wang
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/2767-9764.c.6949335.v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/2767-9764.c.6949335.v1
The cGAS/STING cytosolic DNA-sensing pathway plays a significant role in antitumor immunity. Expression of STING is tightly regulated and commonly reduced or defective in many types of cancer. We have identified SIX4 as a significant regulator of STING expression in colon cancer cells. We showed that knockout of SIX4 decreased STING expression at the mRNA and protein levels while ectopic expression of SIX4 increased STING expression. Depletion of SIX4 led to attenuated STING activation and downstream signaling. Reexpression of SIX4 or ectopic expression of STING in SIX4 knockout cells reversed the effect. Ectopic expression of SIX4 enhanced DMXAA and cGAMP-induced STING activation and downstream signaling. Importantly, decrease of SIX4 expression substantially decreased tumor infiltration of CD8+ T cells and reduced the efficacy of PD-1 antibodies to diminish tumor growth in immune competent mice in vivo. Finally, analysis of The Cancer Genome Atlas colon cancer dataset indicated that tumors with high SIX4 expression were significantly enriched in the Inflammatory Response pathway. SIX4 expression also correlated with expression of multiple IFN-stimulated genes, inflammatory cytokines, and CD8A. Taken together, our results implicate that SIX4 is a principal regulator of STING expression in colon cancer cells, providing an additional mechanism and genetic marker to predict effective immune checkpoint blockade therapy responses.Significance:Our studies demonstrate that SIX4 is an important regulator of STING expression, providing a genetic marker or a therapeutic target to predict or enhance immune checkpoint blockade therapy responses in colon cancer.
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Metadata
- Type
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- Language
- en
- Landing Page
- https://doi.org/10.1158/2767-9764.c.6949335.v1
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- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4389047500Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/2767-9764.c.6949335.v1Digital Object Identifier
- Title
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Data from SIX4 Controls Anti-PD-1 Efficacy by Regulating STING ExpressionWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-11-27Full publication date if available
- Authors
-
Beiyuan Liang, Evan H. Zhang, Zhen Ye, Hayden Storts, Jin Wei, Xinru Zheng, Hannah Hylton, Olivia Zaleski, Xuanxuan Xing, Wayne Miles, Jing J. WangList of authors in order
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https://doi.org/10.1158/2767-9764.c.6949335.v1Publisher landing page
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://doi.org/10.1158/2767-9764.c.6949335.v1Direct OA link when available
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Sting, Ectopic expression, Cancer research, Regulator, Biology, Gene, Genetics, Engineering, Aerospace engineeringTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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