Journal: Cancer Biology & Therapy

Article Title: ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING–IFN suppression

doi: 10.1080/15384047.2026.2632995

Figure Lengend Snippet: ENPP3 is aberrantly high in ccRCC. (A) Box plot showing the distribution of ENPP3 expression in normal kidney tissue ( n = 72) compared to ccRCC tissue ( n = 523). (B) Kaplan–Meier overall survival curves for ccRCC patients stratified by ENPP3 expression levels. (C) Scatter plot showing the relative ENPP3 expression in normal kidney tissue ( n = 100) and ccRCC tissue ( n = 100). (D) Upper panel: Western blot analysis of ENPP3 protein expression in three representative and paired ccRCC tumor and adjacent normal tissue samples. Lower panel: qPCR quantification of ENPP3 mRNA levels in a panel of ccRCC cell lines (Caki-2, ACHN, 786-O, A498, 769-P, RCC4, and SNU-333) and the non-malignant HEK293 control. (E) Representative IHC staining of ENPP3 in normal (left) and ccRCC tissue (right).

Article Snippet: ENPP3-knockdown (shENPP3) or control (shNT) RCC4 xenografts ( n = 3/group) were harvested at day 18; where indicated mice received three i.p. injections of 250 μg neutralizing (WT) STING (TP308418, Origene).

Techniques: Expressing, Western Blot, Control, Immunohistochemistry

Journal: Cancer Biology & Therapy

Article Title: ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING–IFN suppression

doi: 10.1080/15384047.2026.2632995

Figure Lengend Snippet: ENPP3 overexpression promotes tumor growth, and its inhibition enhances the efficacy of immune checkpoint blockade therapy. (A) Tumor growth curves of ACHN cells stably transfected with NC or ENPP3 in a xenograft model. (B) Tumor growth curves of Caki-2 cells stably transfected with NC or ENPP3 in a xenograft model. (C) Tumor growth curves of RCC4 cells stably transfected with shNT or shENPP3 in a xenograft model. (D) Tumor growth curves of SNU-333 cells stably transfected with shNT or shENPP3 in a xenograft model. (E) Pooled individual tumor growth curves for each SNU-333 xenografts ( n = 5 mice per arm) treated with control IgG, anti-PD-L1, anti-ENPP3, or the combination; the same individual data are displayed separately by treatment in the four right-hand panels.

Article Snippet: ENPP3-knockdown (shENPP3) or control (shNT) RCC4 xenografts ( n = 3/group) were harvested at day 18; where indicated mice received three i.p. injections of 250 μg neutralizing (WT) STING (TP308418, Origene).

Techniques: Over Expression, Inhibition, Stable Transfection, Transfection, Control

Journal: Cancer Biology & Therapy

Article Title: ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING–IFN suppression

doi: 10.1080/15384047.2026.2632995

Figure Lengend Snippet: ENPP3 modulates the extracellular cGAMP and immune landscape in ccRCC. (A) Measurement of extracellular and intracellular cGAMP in ACHN and Caki-2 cells transfected with NC or ENPP3. (B) Measurement of extracellular and intracellular cGAMP in RCC4 and SNU-333 cells transfected with shNT or shENPP3. (C) Tumor volume in the RCC4 (ENPP3-intact or knockdown) xenograft model in combination with neutralizing STING administration. (D) Quantification of macrophage infiltration in RCC4 (ENPP3-intact or knockdown) xenograft tumors in combination with neutralizing STING administration. (E) The mean intensity of pIRF3 in M1-like macrophage in RCC4 (ENPP3-intact or knockdown) xenograft tumors in combination with neutralizing STING administration. (F) Quantification of MHC-II hi CD103 + in CD11b − CD11c + cDCs in RCC4 (ENPP3-intact or knockdown) xenograft tumors in combination with neutralizing STING administration. (G) Quantification of CTL activation (CD69 + ) in RCC4 (ENPP3-intact or knockdown) xenograft tumors in combination with neutralizing STING administration. (H) Quantification of CTL activation (CD25 + ) in RCC4 (ENPP3-intact or knockdown) xenograft tumors in combination with neutralizing STING administration. (I) The mean intensity of FOXP3 of CD3 hi CD4 + CD8 − CD45 + population in RCC4 (ENPP3-intact or knockdown) xenograft tumors in combination with neutralizing STING administration.

Article Snippet: ENPP3-knockdown (shENPP3) or control (shNT) RCC4 xenografts ( n = 3/group) were harvested at day 18; where indicated mice received three i.p. injections of 250 μg neutralizing (WT) STING (TP308418, Origene).

Techniques: Transfection, Knockdown, Activation Assay

Journal: Cancer Biology & Therapy

Article Title: ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING–IFN suppression

doi: 10.1080/15384047.2026.2632995

Figure Lengend Snippet: ENPP3 deficiency induces a local type I IFN response in ccRCC. (A) qRT-PCR analysis of Ifnb1 and ISGs in TAMs isolated from RCC4 xenografts treated with shNT or shENPP3. (B) qRT-PCR analysis of Usp18, Oas3, and Ifit1 in PBMCs. (C) Measurement of IFNβ protein levels in RCC4 xenografts treated with shNT or shENPP3. (D–H) Quantitative ELISA analysis of CCL3, CCL4, CCL5, CCL7, and CCL12 in RCC4 xenografts treated with shNT or shENPP3. (I) Pooled individual tumor growth curves for each SNU-333 xenografts ( n = 5 mice per arm) treated with control IgG, anti-ENPP3, anti-IFNAR1, or the combination; the same individual data are displayed separately by treatment in the four right-hand panels.

Article Snippet: ENPP3-knockdown (shENPP3) or control (shNT) RCC4 xenografts ( n = 3/group) were harvested at day 18; where indicated mice received three i.p. injections of 250 μg neutralizing (WT) STING (TP308418, Origene).

Techniques: Quantitative RT-PCR, Isolation, Enzyme-linked Immunosorbent Assay, Control