Immunotherapy with T11TS / S-LFA-3 specifically induces apoptosis of brain tumor cells by augmenting intracranial immune status.
BACKGROUND
Immunopotentiating agents are the best options in cancer therapeutics because they can specifically destroy tumor cells via immunocytes, which are mostly apoptotic in nature. Previously, immunotherapy with T11TS / SLFA-3 in a ethyl-nitrosourea (ENU)-induced animal model (Druckrey rats) of neural neoplasm showed a significant tumor mass destruction by augmenting the cellular immune status.


METHODS
The modulations of the peripheral as well as neural immune systems after T11TS administration were monitored by assessing the CD4+ and CD8+ lymphocytes, along with the cytotoxic activity of splenic and brain infiltrating lymphocytes (BIL). The rate of apoptosis of the tumor cells, microglial cells (Mg) and BIL were measured by flow cytometry-based propidium iodide analysis and TUNEL assay.


RESULTS
Cell cycle phase distribution analysis by propidium iodide -FACS and TUNEL assay revealed that T11TS administration gradually increased the number of apoptotic brain tumor cells and, at the same time, decreased the number of dividing cells. Up-regulation of the CD4+ and CD8+ lymphocytes were observed after T11TS administration in ENU - induced immunosuppressed animals. A gradual increment of cytotoxicity of splenic and BIL was also demonstrated after successive administration of T11TS.


CONCLUSIONS
These data strongly support the specific apoptosis-inducing role of T11TS in experimental brain tumor cells. Apoptosis of BIL and Mg, that occurred to a much lower level, can be explained in terms of changes in the neural immune system before and after T11TS application.
Mukherjee
Joydeep
J
Cellular and Molecular Immunology Laboratory, Department of Physiology, Dr. B. C. Roy Postgraduate Institute of Basic Medical Sciences, 244 B, A. J. C. Bose Road, Kolkata - 700 020, West Bengal, India.
Ghosh
Anirban
A
Sarkar
Pallab
P
Mazumdar
Malabika
M
Banerjee
Chandra
C
Chaudhuri
Swapna
S
D000818:Animals; D001921:Brain / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016516:CD4-CD8 Ratio; D018968:CD58 Antigens / Q000276:immunology / Q000494:pharmacology*; D002453:Cell Cycle / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005434:Flow Cytometry; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods; D020287:In Situ Nick-End Labeling; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology; D051381:Rats; D013154:Spleen / Q000276:immunology
D018968:CD58 Antigens; D007155:Immunologic Factors