Kumari Smita, Sahu Srishti, Singh Bharat, Gupta Swarnima, Kureel Amit Kumar, Srivastava Ankit, Rikhari Deeksha, Srivastava Sameer, Rai Ambak Kumar
Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad (M.N.N.I.T. Allahabad), Prayagraj, Uttar Pradesh 211004, India.
Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad (M.N.N.I.T. Allahabad), Prayagraj, Uttar Pradesh 211004, India.
Cell Immunol. 2023 Sep-Oct;391-392:104755. doi: 10.1016/j.cellimm.2023.104755. Epub 2023 Aug 1.
CD5, 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.
CD5是一种T细胞受体（TCR）负调节因子，在肿瘤微环境（TME）中，其在CD8+淋巴细胞表面的表达减少。表面CD5表达（sCD5）降低是由于人内源性逆转录病毒-E（HERV-E）衍生的外显子E1B的优先转录，即cd5基因的一种非传统形式，而非其传统外显子E1A。肿瘤采用多种机制逃避免疫抗肿瘤反应，缺氧就是其中一种在TME中普遍存在并调节浸润性T淋巴细胞的机制。我们在E1B上游鉴定出缺氧反应元件（HREs）。我们发现缺氧诱导因子-1α（HIF-1α）与这些HREs结合，并增加缺氧T细胞中E1B mRNA的表达。这导致T细胞中sCD5表达降低和细胞质积累增加。我们还在实体瘤，即结直肠癌（CRC）患者样本中验证了我们的研究。这种缺氧驱动的机制降低了实体瘤中浸润性T细胞表面CD5的表达。
