ArticleInternational journal of molecular sciences2023
The Regulatory Axis of PD-L1 Isoform 2/TNF/T Cell Proliferation Is Required for the Canonical Immune-Suppressive Effects of PD-L1 Isoform 1 in Liver Cancer.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
1 citing paper in PubMed, 1 citations in OpenAlex.
- A splicing isoform of PD-1 promotes tumor progression as a potential immune checkpoint.Nature communications · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Despite the well-studied effects of the full-length membrane-locating isoform Iso1 of Programmed Cell Death Protein-Ligand 1 (PD-L1) on immunosuppression, little is known about another membrane-locating isoform, Iso2. While expressional and survival analysis of liver cancer patients indicated that Iso2 plays a tumor-suppressive role, our results also indicated that the tumor-promoting and immune-suppressive effects of Iso1 depended on the positive expression of Iso2. Through mediation analysis, we discovered several downstream genes or pathways of Iso2 and investigated their effects on the Iso1-regulating survival. Among all potential downstream immune factors, Iso2 was inclined to activate the proliferation of T cells by regulating chemokine activity and increasing CD3 levels by promoting TNF expression. Similar results were confirmed in the Mongolian liver cancer cohort, and the Iso2/TNF/T-cell axis was verified in several other cancers in the TCGA cohort. Finally, we demonstrated the promoting effects of Iso2 in terms of producing TNF and increasing T cells both in vitro and in vivo. Our findings illustrate that PD-L1 Iso2 can increase the number of T cells in the tumor microenvironment by elevating TNF levels, which is a necessary part of the tumor-suppressive effects of Iso1 in liver cancer.
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Registered trials
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