title: Neem leaf glycoprotein activates CD8(+) T cells to promote therapeutic anti-tumor immunity inhibiting the growth of mouse sarcoma.
abstract: In spite of sufficient data on Neem Leaf Glycoprotein (NLGP) as a prophylactic vaccine, little knowledge currently exists to support the use of NLGP as a therapeutic vaccine. Treatment of mice bearing established sarcomas with NLGP (25 µg/mice/week subcutaneously for 4 weeks) resulted in tumor regression or dormancy (Tumor free/Regressor, 13/24 (NLGP), 4/24 (PBS)). Evaluation of CD8(+) T cell status in blood, spleen, TDLN, VDLN and tumor revealed increase in cellular number. Elevated expression of CD69, CD44 and Ki67 on CD8(+) T cells revealed their state of activation and proliferation by NLGP. Depletion of CD8(+) T cells in mice at the time of NLGP treatment resulted in partial termination of tumor regression. An expansion of CXCR3(+) and CCR5(+) T cells was observed in the TDLN and tumor, along with their corresponding ligands. NLGP treatment enhances type 1 polarized T-bet expressing T cells with downregulation of GATA3. Treg cell population was almost unchanged. However, T∶Treg ratios significantly increased with NLGP. Enhanced secretion/expression of IFNγ was noted after NLGP therapy. In vitro culture of T cells with IL-2 and sarcoma antigen resulted in significant enhancement in cytotoxic efficacy. Consistently higher expression of CD107a was also observed in CD8(+) T cells from tumors. Reinoculation of sarcoma cells in tumor regressed NLGP-treated mice maintained tumor free status in majority. This is correlated with the increment of CD44(hi)CD62L(hi) central memory T cells. Collectively, these findings support a paradigm in which NLGP dynamically orchestrates the activation, expansion, and recruitment of CD8(+) T cells into established tumors to operate significant tumor cell lysis.
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), Kolkata, India.
authors: Atanu
authors: A
authors: Mallick
authors: Subhasis
authors: S
authors: Barik
authors: Kuntal Kanti
authors: KK
authors: Goswami
authors: Saptak
authors: S
authors: Banerjee
authors: Sarbari
authors: S
authors: Ghosh
authors: Koustav
authors: K
authors: Sarkar
authors: Anamika
authors: A
authors: Bose
authors: Rathindranath
authors: R
authors: Baral
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000494:pharmacology; D031601:Azadirachta / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018515:Plant Leaves / Q000737:chemistry / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology* / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; C515188:Cxcr3 protein, mouse; D006023:Glycoproteins; D010940:Plant Proteins; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D007371:Interferon-gamma