title: The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation.
abstract: T-cell-mediated immune responses are typically low in conditions of malignant glioma which has been known to cause marked immunesuppression and dysregulate major T-cell signaling molecules. Thus, T-cell-based immunotherapies are currently in vogue in the treatment of malignant glioma. The novel glycopeptide, T11TS/S-LFA-3/S-CD58 has previously been shown by our group to be highly efficacious in glioma abrogation in in vivo and in vitro conditions. This glycopeptide ligands to the costimulatory CD2 molecule on T-cells, causing profound immune stimulation leading to glioma abrogation, suggesting probable involvement of T11TS in modulation of the T-cell signaling pathway. The present study offers a multi-targeted approach towards repair of some of the key components of the immunological synapse at the T-cell-APC interface and is therefore the first of its kind to offer a holistic model of restoration of immunological synapse components so as to trigger T-cells towards activation against glioma. The study thus indicates that the totally dysregulated molecular events at the immunological synapse in glioma are restored back to normal levels with the administration of T11TS, which finally culminates in glioma abrogation. The present study thus delineates an important T-cell signaling approach whereby T11TS acts as an anti-neoplastic agent, thus helping to chart out newer avenues in the fight against gliomas.
authors.affiliation: Department of Laboratory Medicine, School of Tropical Medicine, Cellular and Molecular Immunology Lab, 108, C. R. Avenue, Kolkata, 700073, West Bengal, India.
authors.forename: Suhnrita
authors.initials: S
authors.lastname: Chaudhuri
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Singh
authors.forename: Debanjan
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Sagar
authors.initials: S
authors.lastname: Acharya
authors.forename: Sirshendu
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.forename: Pushpak
authors.initials: P
authors.lastname: Bhattacharjee
authors.forename: Anjan Kumar
authors.initials: AK
authors.lastname: Basu
authors.forename: Gaurisankar
authors.initials: G
authors.lastname: Sa
authors.forename: Tanya
authors.initials: T
authors.lastname: Das
authors.forename: Tushar Kanti
authors.initials: TK
authors.lastname: Ghosh
authors.forename: Swapna
authors.initials: S
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism*; D018968:CD58 Antigens / Q000276:immunology / Q000378:metabolism*; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D006020:Glycopeptides / Q000627:therapeutic use*; D054992:Immunological Synapses / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D018801:CD2 Antigens; D018968:CD58 Antigens; D006020:Glycopeptides; D009153:Mutagens; D005038:Ethylnitrosourea