GSK-3 inhibitor elraglusib enhances tumor-infiltrating immune cell activation in tumor biopsies and synergizes with anti-PD-L1 in a murine model of colorectal cancer

GSK-3 抑制剂 elraglusib 可增强肿瘤活检中的肿瘤浸润免疫细胞活化,并在小鼠结肠直肠癌模型中与抗 PD-L1 产生协同作用

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作者:Kelsey E Huntington, Anna D Louie, Praveen R Srinivasan, Christoph Schorl, Shaolei Lu, David Silverberg, Daniel Newhouse, Zhijin Wu, Lanlan Zhou, Brittany A Borden, Francis J Giles, Mark Dooner, Benedito A Carneiro, Wafik S El-Deiry

Significance

Pharmacologic inhibition of GSK-3 using elraglusib sensitizes tumor cells, activates immune cells for increased anti-tumor immunity, and synergizes with anti-PD-L1 immune checkpoint blockade. These results introduce novel biomarkers for correlations with response to therapy which could provide significant clinical utility and suggest that elraglusib, and other GSK-3 inhibitors, should be evaluated in combination with immune checkpoint blockade.

Statement of significance

Pharmacologic inhibition of GSK-3 using elraglusib sensitizes tumor cells, activates immune cells for increased anti-tumor immunity, and synergizes with anti-PD-L1 immune checkpoint blockade. These results introduce novel biomarkers for correlations with response to therapy which could provide significant clinical utility and suggest that elraglusib, and other GSK-3 inhibitors, should be evaluated in combination with immune checkpoint blockade.

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