Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by differentially regulating cytotoxic
Madhurima Sarkar1, Sarbari Ghosh1, Avishek Bhuniya1
1Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), Kolkata 700026, India.
Abstract:
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.
Insights
Neem leaf glycoprotein (NLGP) prevents sarcoma recurrence post-surgery by boosting cytotoxic CD8+ T cells and reducing suppressor cells. This immunotherapy enhances tumor-free survival in mice.
Area of Science:
- Immunology
- Cancer Biology
- Pharmacology
Background:
- Post-surgical tumor recurrence remains a significant challenge in cancer treatment.
- Neem leaf glycoprotein (NLGP) is identified as a novel immunomodulator with potential therapeutic applications.
Purpose of the Study:
- To investigate the efficacy of NLGP in preventing post-surgical recurrence of solid sarcoma.
- To elucidate the immunomodulatory mechanisms underlying NLGP's anti-tumor effects.
Main Methods:
- Surgical removal of sarcoma in Swiss mice followed by NLGP administration.
- Flow cytometry analysis to assess immune cell populations (CD8+ T cells, MDSCs).
- In vivo CD8+ T cell depletion experiments to confirm their role in NLGP's efficacy.
Main Results:
- NLGP treatment significantly prevented tumor recurrence and increased tumor-free survival time.
- NLGP administration led to an increase in cytotoxic CD8+ T cells and a decrease in myeloid-derived suppressor cells (MDSCs).
- CD8+ T cell activation by NLGP was crucial for downregulating MDSCs and restoring immune surveillance.
Conclusions:
- NLGP demonstrates potent anti-cancer properties by modulating the immune response against residual tumor cells.
- NLGP activates CD8+ T cells, which in turn suppress MDSCs, thereby overcoming immune suppression and preventing tumor recurrence.
- NLGP represents a promising therapeutic strategy for preventing post-surgical cancer recurrence.
