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.