Disease relevance of RAET1E

• Letal was found to be an independent prognosticator of improved survival in advanced ovarian cancer [1].
• Inflammatory polyradiculoneuropathy with spinal cord involvement and lethal [correction of letal] outcome after hepatitis B vaccination [2].
• Extracts of increasing polarity of 6 Venezuelan plants belonging to the Chrysobalanaceae family were tested for possible letal toxicity against Biomphalaria glabrata Say, a snail intermediate hosts of Schistosoma mansoni Sambon [3].

High impact information on RAET1E

• Ovarian carcinoma expresses the NKG2D ligand Letal and promotes the survival and expansion of CD28- antitumor T cells [1].
• Higher levels of tumor-derived Letal were associated with stronger lymphocyte infiltration [1].
• Human ovarian carcinoma expresses the novel NKG2D ligand lymphocyte effector cell toxicity-activating ligand (Letal) [1].
• Letal exerted marked costimulatory effects and induced type-1 polarization in CD8+CD28- tumor-infiltrating lymphocytes ex vivo [1].
• Letal also down-regulated the expression of Fas in CD8+ cells and rendered them resistant to Fas ligand-induced apoptosis [1].

Biological context of RAET1E

• We characterized two novel members of the RAET1/ULBP gene cluster, RAET1E and RAET1G [4].
• Whereas MICA, ULBP1/3 and RAET1-E did not display heightened gene expression, elevated levels of NKG2D mRNA could be associated with aRx (p < 0.001) [5].
• They may induce cell membrane lipid peroxidation, with non reversible letal effects [6].

Anatomical context of RAET1E

• In addition, Letal induced the killing of cancer cells by CD8(+) and NK cells [7].

Associations of RAET1E with chemical compounds

• Letal engagement increased the expression of the glucose transporter Glut-1, enhanced glucose up-take, and protected CD8+ lymphocytes from cisplatin-induced killing [1].
• Unlike other NKG2D ligands, Letal mRNA expression progressively decreased after treatment of tumor cells with retinoic acid [7].
• The synthetic peptides consisted, respectively, of residues 59-81 of the human surfactant protein SP-B and 21 amino acid residue peptides containing repeating units of arginine separated by either four or eight leucines (RL4 or RL8) [8].

Other interactions of RAET1E

• ULBP4 is a novel ligand for human NKG2D [9].

Analytical, diagnostic and therapeutic context of RAET1E

• We propose that Letal could be used for the ex vivo expansion of apoptosis-resistant tumor-reactive cytotoxic lymphocytes for adoptive transfer [1].
• Particularly in the biologic therapy of cancer, identifiable antigenic T-cell targets restricted by MHC molecules and the related novel stress molecules such as MICA/B and Letal allow a degree of precision previously unknown in cancer therapy [10].

References