AI Article Synopsis
- NPRL2, a tumor suppressor, is often downregulated in glioma, leading to aggressive tumor growth and unclear interactions with immune cells.
- The study investigates how NPRL2 influences the degradation of Galectin-3 (Gal-3) via TRIM16, affecting immune cell functions and copper uptake in CD8T lymphocytes.
- Results show that NPRL2 enhances TRIM16 expression and reduces Gal-3 levels, which improves CD8T cell recruitment and protects them from Gal-3-related damage, suggesting a potential therapeutic target for restoring immune function in glioma.
Article Abstract
Background: Our previous study found that tumor suppressor nitrogen permease regulator like-2(NPRL2) is frequently downregulated in glioma, leading to malignant growth. However, NPRL2-mediated crosstalk between tumor cells and immune cells remains unclear.
Methods: The regulatory effects of NPRL2 on tripartite motif-containing protein 16(TRIM16) dependent ubiquitination degradation of Galectin-3(Gal-3) were explored. The effects of Gal-3 on copper uptake, immunocompetence and cuproptosis were investigated in CD8T lymphocytes(CD8T cells). The ability of NPRL2 to protect CD8T cells from Gal-3 damage was evaluated. Furthermore, the correlations among NPRL2, TRIM16, Gal-3 and CD8T cell accumulation were analyzed in glioma clinical specimens.
Results: NPRL2 increased the TRIM16 expression via inactivation of ERK1/2, which in turn promoted the ubiquitination-mediated degradation of Gal-3 and diminished Gal-3 release from glioma cells. Moreover, Gal-3 accelerated copper uptake and triggered cuproptosis in CD8T cells, whereas NPRL2 increased CD8T cell recruitment and prevented impairment of CD8T cells by Gal-3. Clinical samples revealed that NPRL2 expression was positively associated with TRIM16 expression and negatively correlated with Gal-3, but Gal-3 expression was negatively associated with CD8T cell accumulation.
Conclusion: Glioma-derived NPRL2/TRIM16/Gal-3 axis participates in the regulation of CD8T cell cuproptosis, which provides a promising strategy to rescue the immune activity of CD8T cells and reverse immunosuppression in glioma.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456027 | PMC |
| http://dx.doi.org/10.1007/s00018-024-05454-2 | DOI Listing |
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