title: Neem leaf glycoprotein promotes dual generation of central and effector memory CD8(+) T cells against sarcoma antigen vaccine to induce protective anti-tumor immunity.
abstract: We have previously shown that Neem Leaf Glycoprotein (NLGP) mediates sustained tumor protection by activating host immune response. Now we report that adjuvant help from NLGP predominantly generates CD44(+)CD62L(high)CCR7(high) central memory (TCM; in lymph node) and CD44(+)CD62L(low)CCR7(low) effector memory (TEM; in spleen) CD8(+) T cells of Swiss mice after vaccination with sarcoma antigen (SarAg). Generated TCM and TEM participated either to replenish memory cell pool for sustained disease free states or in rapid tumor eradication respectively. TCM generated after SarAg+NLGP vaccination underwent significant proliferation and IL-2 secretion following SarAg re-stimulation. Furthermore, SarAg+NLGP vaccination helps in greater survival of the memory precursor effector cells at the peak of the effector response and their maintenance as mature memory cells, in comparison to single modality treatment. Such response is corroborated with the reduced phosphorylation of FOXO in the cytosol and increased KLF2 in the nucleus associated with enhanced CD62L, CCR7 expression of lymph node-resident CD8(+) T cells. However, spleen-resident CD8(+) T memory cells show superior efficacy for immediate memory-to-effector cell conversion. The data support in all aspects that SarAg+NLGP demonstrate superiority than SarAg vaccination alone that benefits the host by rapid effector functions whenever required, whereas, central-memory cells are thought to replenish the memory cell pool for ultimate sustained disease free survival till 60 days following post-vaccination tumor inoculation.
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Sarbari
authors: S
authors: Ghosh
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Madhurima
authors: M
authors: Sarkar
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Tithi
authors: T
authors: Ghosh
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Ipsita
authors: I
authors: Guha
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Avishek
authors: A
authors: Bhuniya
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Akata
authors: A
authors: Saha
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Shayani
authors: S
authors: Dasgupta
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Subhasis
authors: S
authors: Barik
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors: Anamika
authors: A
authors: Bose
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address: baralrathin@hotmail.com.
authors: Rathindranath
authors: R
authors: Baral
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D031601:Azadirachta / Q000276:immunology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000276:immunology; D018515:Plant Leaves / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006023:Glycoproteins; D010936:Plant Extracts; D010940:Plant Proteins; C412325:SAGE1 protein, human
keywords: Central memory CD8(+) T cells; Effector memory cells; FOXO; KLF2; Neem leaf glycoprotein; Sarcoma antigen