Interaction between endothelial cells and the secreted cytokine drives thefate of an IL4- or an IL5-transduced tumour

Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngenei c immunocompetent mice resulted in tumour rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits tumour growth by selectively inducing eosinophil recruitment and activation, a poorly dif ferentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL4) were injected subcutaneousl y (s.c.) in syngeneic mice, The oncogenicity of TSA-IL5 was compared with t hat exhibited by TSA cells transfected with the IL4 gene (TSA-IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after su bcutaneous challenge, tumour growth areas were studied histologically, ultr astructurally, and immunohistochemically to identify the reactive cells, vi sualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data s howed that TSA-IL5, despite the large eosinophil infiltrate, grew progressi vely like TSA-neo, suggesting that eosinophils pel se do not play a crucial role in TSA tumour rejection, Furthermore, our data indicate that the reje ction of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells, MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-infl ammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection, In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a con tinuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils, (C) 1998 John Wi ley & Sons, Ltd.