Effect of thymosin alpha 1 on the antitumor activity of tumor-associated macrophage-derived dendritic cells.
We have previously suggested that thymosin alpha(1) (thyalpha1), an immunomodulating thymic hormone, can activate tumor-associated macrophages to a tumoricidal state in a murine model bearing a transplantable T-cell lymphoma of spontaneous origin designated as Dalton's lymphoma (DL). Since tumor-infiltrating dendritic cells (DC) also play an important role in the host's antitumor response and are as such in an immunocompromised state in a tumor-bearing host, in the present investigation we studied if thyalpha1 is able to influence the differentiation of tumor-associated macrophages (TAM) into DC with granulocyte macrophage colony stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF) and whether these TAM-derived DC show enhanced antitumor activity. It was observed that DC generated from thyalpha1-administered tumor-bearing mice showed augmented antitumor activity in vitro. Adoptive immunotherapy using TAM-derived DC showed a significant delay in the tumor growth and a prolongation of the survival time in tumor-bearing mice. DC obtained from TAM of thyalpha1-administered mice also produced an enhanced amount of cytokines like IL-1 and TNF-alpha. This is the first study of its kind regarding the effect of thyalpha1 on the differentiation of DC from TAM and the role of TAM-derived DC in tumor progression.
School of Biotechnology, Banaras Hindu University, Varanasi, India.
Pratima
P
Shrivastava
Sukh Mahendra
SM
Singh
Nisha
N
Singh
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology*; D009573:Nitrites / Q000378:metabolism; D010873:Pinocytosis; D013601:T-Lymphocytes / Q000276:immunology; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D013947:Thymosin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000077596:Thymalfasin