Neem leaf glycoprotein promotes dual generation of central and effector memory CD8 + T cells against sarcoma antigen vaccine to induce protective anti-tumor immunity

Ghosh, Sarbari; Sarkar, Madhurima; Ghosh, Tithi; Guha, Ipsita; Bhuniya, Avishek; Saha, Akata; Dasgupta, Shayani; Barik, Subhasis; Bose, Anamika; Baral, Rathindranath

doi:10.1016/j.molimm.2016.01.007

Cited by 18 publications

(18 citation statements)

References 46 publications

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“…As tumor recurrence depends on host immunity and NLGP restricts mouse tumor growth in a CD8 + T-cell-dependent manner [16,37,38], further the involvement of CD8 + T cells in post-surgical prevention of tumor recurrence by NLGP was checked. Assessment of circulating CD8 + T cells from the blood of PBS and NLGP immunized mice at different time points was done before and after surgical removal of the mice tumor.…”

Section: Resultsmentioning

confidence: 99%

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

Sarkar¹,

Ghosh²,

Bhuniya³

et al. 2017

PLoS ONE

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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.

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Section: Resultsmentioning

confidence: 99%

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

Sarkar¹,

Ghosh²,

Bhuniya³

et al. 2017

PLoS ONE

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“…It also helps in the maturation of myeloid and mouse bone marrow derived dendritic cells providing efficient antigen presentation as well as co-stimulation of effector T cells (Goswami et al, 2010) indicating it's potential as a candidate for vaccine tool toward cancer immunotherapy. Recently, it was also established that a combination of NLGP with sarcoma antigen (SarAg) vaccination demonstrates anti-tumor immunity which had high superiority as compared to the SarAg vaccination alone since, the inoculation of the vaccination presented disease free survival until 60 days (Ghosh et al, 2016). …”

Section: Procedures For the Extraction Of Neem Functional Ingredientsmentioning

confidence: 99%

Progress on Azadirachta indica Based Biopesticides in Replacing Synthetic Toxic Pesticides

et al. 2017

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Over the years, extensive use of commercially available synthetic pesticides against phytophagous insects has led to their bioaccumulation in the environment causing increased resistance and reduction in soil biodiversity. Further, 90% of the applied pesticides enter the various environmental resources as a result of run-off, exposing the farmers as well as consumers of the agricultural produce to severe health issues. Therefore, growing attention has been given toward the development of alternate environmentally friendly pesticides/insecticides that would aid an efficient pest management system and also prevent chronic exposures leading to diseases. One such strategy is, the use of neem plant's (Binomial name: Azadirachta indica) active ingredients which exhibit agro-medicinal properties conferring insecticidal as well as immunomodulatory and anti-cancer properties. The most prominent constituent of neem is azadirachtin, which has been established as a pivotal insecticidal ingredient. It acts as an antifeedant, repellent, and repugnant agent and induces sterility in insects by preventing oviposition and interrupting sperm production in males. This review discusses, key neem pesticidal components, their active functional ingredients along with recent strategies on employing nanocarriers, to provide controlled release of the active ingredients and to improve their stability and sustainability.

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“…On the other hand, several plant based natural molecules or anti-oxidants show promises in reducing VEGF but their mechanisms are largely unknown. Neem leaf glycoprotein (NLGP), a non-toxic immune-modulator, show sustained tumor growth restriction in multiple murine cancer settings primarily by activating CD8 + cytotoxic T cells (19,20). We also reported normalization of aberrant angiogenesis in murine carcinoma and melanoma hosts in an immune dependent manner (21).…”

Section: Introductionmentioning

confidence: 83%

“…Tumors were fixed to stain with VEGF according to method described (19). In some cases, VEGF positive regions were selected and dissected using laser capture microscopy.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

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Neem Leaf Glycoprotein Restrains VEGF Production by Direct Modulation of HIF1α-Linked Upstream and Downstream Cascades

et al. 2020

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Neem leaf glycoprotein promotes dual generation of central and effector memory CD8 + T cells against sarcoma antigen vaccine to induce protective anti-tumor immunity

Cited by 18 publications

References 46 publications

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

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

Progress on Azadirachta indica Based Biopesticides in Replacing Synthetic Toxic Pesticides

Neem Leaf Glycoprotein Restrains VEGF Production by Direct Modulation of HIF1α-Linked Upstream and Downstream Cascades

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