Neem leaf glycoprotein matures myeloid derived dendritic cells and optimizes anti-tumor T cell functions.
In an objective to find out an effective, nontoxic dendritic cell (DC) maturating agent for human use, CD14(+) monocytes were differentiated with GMCSF/IL-4 and matured with neem leaf glycoprotein (NLGP). NLGP matured DCs (NLGP-DCs) show upregulated expression of CD83, CD80, CD86, CD40 and MHCs, in a comparable extent of control, LPS. NLGP-DCs secrete high amount of IL-12p70 with low IL-10. NLGP upregulates the expression of crucial transcription factor, ikaros, indicating maturation towards DC1 phenotype. Increased expression of CD28 and CD40L on T cells following co-culture with NLGP-DCs was noticed to promote DC-T interactions. As a result, T cells secrete high amount of IFN gamma with low IL-4 and generates anti-tumor type 1 immune microenvironment. Such NLGP-DCs present carcinoembryonic antigen (CEA) effectively to T cells to increase T cell mediated cytotoxicity of CEA(+) tumor cells in vitro and in vivo. With emergence of the NLGP as a promising DC maturating agent, NLGP-DCs can be used as a candidate vaccine tool for antigen specific cancer immunotherapy.
Goswami
Shyamal
S
Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, West Bengal 700026, India.
Bose
Anamika
A
Sarkar
Koustav
K
Roy
Soumyabrata
S
Chakraborty
Tathagata
T
Sanyal
Utpal
U
Baral
Rathindranath
R
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D031601:Azadirachta; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D018515:Plant Leaves; D010940:Plant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D006023:Glycoproteins; D010940:Plant Proteins; D016753:Interleukin-10; D018664:Interleukin-12