An Eosinophil-Dependent Mechanism for the Antitumor Effect of Interleukin-4

Abstract

Murine interleukin-4 (IL-4) exhibits potent antitumor activity when present at the site of tumor cell challenge. Associated with tumor cell death is the appearance of an inflammatory infiltrate comprised predominantly of eosinophils and macrophages, but with few lymphocytes. Antibodies that specifically block the accumulation of granulocytes at the site of inflammation were injected in vivo to define the cell type responsible for the antitumor action of IL-4. These studies implicate eosinophils in IL-4-mediated tumor cytotoxicity. The lymphoid-independent nature of IL-4 action is supported by the analysis of mutant mouse strains with defined lymphocyte immunodeficiencies. The observed regression of established tumor masses by localized IL-4 action provides a rationale for exploring IL-4-mediated tumor killing as a potential therapy for human malignant disorders.

Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

“…8 The IL-4-activated tumor inhibition is a consequence of the macrophage and eosinophil infiltration. 8,22,33,34 Host T cells are also involved in the induction and effector phase of IL-4-activated tumor rejection with the antigen non-specific cells predominating. 4,8,22 In this study we have demonstrated that the membrane-bound versions of IL-4 expressed on tumor cells are biologically functional.…”

Paradoxical Roles of IL-4 in Tumor Immunity

“…In fact, besides eosinophils, neutrophils were also present at IL-4-producing tumor site (6). The antigen recognized by RB6-8C5 is expressed on both eosinophils and neutrophils (22). In the cell-depletion experiments performed by Tepper, RB6-8C5 treatment simultaneously depleted eosinophils and neutrophils.…”

“…This type of cells, as well as macrophages, existed in abundant amount in IL-4 secreting tumor site. Depletion of eosinophils using the mAb RB6-8C5 (Anti-Gr1, a myeloid differentiation antigen) restored the growth of IL-4-secreting tumor in BALB/c mice (22). However, the idea of considering eosinophils as the primary effectors encountered a little trouble when people found that tumor cells engineered to secrete IL-5 induced abundant eosinophil infiltration, but could not be rejected (23).…”

Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines

“…The neutrophil-depleting mAb RB6-8C5 was a kind gift from Dr. Robert L. Coffman [11] and was affinity-purified from culture supernatant over a Protein G column (Pharmacia, Uppsala, Sweden). For neutrophil depletion in vivo, mice were treated i.p.…”

“…Some in vitro studies have suggested direct mycobacteriocidal effects of PMN on M. tuberculosis in culture [6][7][8][9], which were disputed by others [10]. In vivo studies in mice after experimental depletion of PMN with the mAb RB6-8C5 [11] and subsequent systemic M. tuberculosis infection revealed a subordinate contribution of PMN to anti-mycobacterial control: survival and mycobacterial titers were comparable between PMN-depleted and non-depleted mice [12,13]. The lack of impact of PMN on the anti-mycobacterial control could be explained by incomplete activation of the PMN by mycobacteria, since PMN from mice as well as from humans failed to generate an oxidative burst upon phagocytosis of mycobacteria [12].…”