TRIM28 drives immune evasion via PARP1 SUMOylation and NAD⁺ depletion in clear cell renal cell carcinoma.

ABSTRACT:

Background

Immune checkpoint blockade (ICB) therapy has demonstrated significant clinical potential in a variety of cancers; however, its efficacy in clear cell renal cell carcinoma (ccRCC) remains suboptimal. In ccRCC, an increased infiltration of CD8⁺ T cells does not necessarily correlate with improved prognosis, indicating the presence of unique immune evasion mechanisms within the tumor microenvironment (TME).

Methods

Tripartite motif-containing 28 (TRIM28) was identified as a potential therapeutic target through single-cell transcriptomics (GSE159115) and Geneformer-based perturbation screening. Functional validation was performed by constructing shTRIM28 and overexpression cell models to assess tumor proliferation, CD8⁺ T cell co-cultures, flow c

SUBMITTER: Zhan X 

PROVIDER: S-EPMC12557765 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature