Résumé
Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.
Résumé
Patients treated with radiotherapy (RT) might experience a large variation in normal tissues. Severe radiation damage in a minority of patients limits the doses that might be safe given to the majority. The possibility of predicting such radiation-induced damage would provide a better treatment schedule for the patients. Several predictive tests in peripheral blood lymphocytes such as initial DNA damage, radiation-induced apoptosis and genetic variation have been proposed to know the individual sensitivity of patients to the radiotherapy schedules. This study aimed to summarize the main studies regarding to this ifeld.