HIF-1 α regulates the expression of the non-conventional isoform of the cd5 gene in T cells under the hypoxic condition: A potential mechanism for CD5 < sup > neg/low < /sup > phenotype of infiltrating cells in solid tumors

Cell Immunol. 2023 Aug 1;391-392:104755. doi: 10.1016/j.cellimm.2023.104755. Online ahead of print.ABSTRACTCD5, a T-cell receptor (TCR) negative regulator, is reduced on the surface of CD8+ lymphocytes in the tumor microenvironment (TME). Reduced surface CD5 expression (sCD5) occurs due to the preferential transcription of HERV-E derived exon E1B, i.e., anon-conventional formofthe cd5gene instead of its conventional exon E1A. A tumor employs several mechanisms to evade anti-tumor response, and hypoxia is one such mechanism that prevails in the TME and modulates the infiltrated T lymphocytes. We identified hypoxia response elements (HREs) upstream of E1B. We showed binding of HIF-1α onto these HREs and increased E1B mRNA expression in hypoxic T cells. This results in decreased sCD5 expression and increased cytoplasmic accumulation in T cells. We also validated our study in a solid tumor, i.e., colorectal cancer (CRC) patient samples. This hypoxia-driven mechanism reduces the surface CD5 expression on infiltrated T-cells in solid tumors.PMID:37544247 | DOI:10.1016/j.cellimm.2023.104755
Source: Cellular Immunology - Category: Allergy & Immunology Authors: Source Type: research