Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by differentially regulating cytotoxic T and myeloid-derived suppressor cells

• Published in: PloS one Vol. 12; no. 4; p. e0175540
• Main Authors: Sarkar, Madhurima, Ghosh, Sarbari, Bhuniya, Avishek, Ghosh, Tithi, Guha, Ipsita, Barik, Subhasis, Biswas, Jaydip, Bose, Anamika, Baral, Rathindranath
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-04-2017; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Apoptosis; Azadirachta - chemistry; Biocompatibility; Biology and life sciences; Cancer recurrence; Cancer therapies; Care and treatment; Caspase 3 - metabolism; Caspase 8 - metabolism; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity; Dendritic cells; Down-Regulation - drug effects; Down-Regulation - immunology; Female; Glycoproteins; Glycoproteins - immunology; Glycoproteins - pharmacology; Immune response; Immune system; Immunization; Immunoglobulins; Immunotherapy; Laboratory animals; Lymphocytes; Lymphocytes T; Medicine and health sciences; Melanoma; Mice; Myeloid-Derived Suppressor Cells - drug effects; Myeloid-Derived Suppressor Cells - immunology; Neem; Neoplasm Recurrence, Local - prevention & control; Physiological aspects; Plant Leaves - chemistry; Plant Proteins - immunology; Plant Proteins - pharmacology; Prevention; Properties; Research and Analysis Methods; Sarcoma; Sarcoma - drug therapy; Sarcoma - immunology; Sodium; Surgery; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Toxicity; Tumor removal; Tumors; Vaccines; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0175540

Post-surgical tumor recurrence is a common problem in cancer treatment. In the present study, the role of neem leaf glycoprotein (NLGP), a novel immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was examined. Data suggest that NLGP prevents tumor recurrence after surgical removal of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP-treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased population of suppressor cells, especially myeloid-derived suppressor cells (MDSCs) was observed. NLGP-treated CD8+ T cells showed greater cytotoxicity towards tumor-derived MDSCs and supernatants from the same CD8+ T cell culture caused upregulation of FasR and downregulation of cFLIP in MDSCs. To elucidate the role of CD8+ T cells, specifically in association with the downregulation in MDSCs, CD8+ T cells were depleted in vivo before NLGP immunization in surgically tumor removed mice and tumor recurrence was noted. These mice also exhibited increased MDSCs along with decreased levels of Caspase 3, Caspase 8 and increased cFLIP expression. In conclusion, it can be stated that NLGP, by activating CD8+ T cells, down regulates the proportion of MDSCs. Accordingly, suppressive effects of MDSCs on CD8+ T cells are minimized and optimum immune surveillance in tumor hosts is maintained to eliminate the residual tumor mass appearing during recurrence.