Abstract
Blood eosinophilia in tumor patients treated with interleukin-2 (IL-2) is well known and is regarded as evidence of toxicity or as a side-effect [Lotze et al. (1986) Arch Surg 121:1373–1379; West et al. (1987) N Engl J Med 316:898–905]. We recently described a new local IL-2 approach to therapy for advanced bladder carcinoma that allows, for the first time, high-dose continuous adminstration of natural interleukin-2 (nIL-2) at the tumor site without side-effects [Huland and Huland (1989) Cancer Res 49:5469–5474]. Tumor-associated eosinophilia of up to 65% (i.e. eosinophils constituting 65% of leukocytes) was seen in four of five patients after treatment, but never before treatment or in untreated controls. Activated eosinophils were attached to bladder tumor cells. Local activation was seen only after natural IL-2 treatment and was determined by cytological criteria and by staining with monoclonal antibody (mAb) EG1 directed against all eosinophil granule proteins and mAb EG2 directed against the active secretory granule proteins of the eosinophils. Bladder cancer cells in urinary sediment also stained with these two mAbs, revealing active degranulation of eosinophils on bladder tumor cells. The number of eosinophils in blood increased, however, without signs of activation. These data constitute strong evidence that activated eosinophils in vivo are involved in the IL-2-induced antitumor response.
Key words: Topical interleukin-2, Eosinophilia, Eosinophil cytotoxicity, Bladder cancer
Abbreviations
- nIL-2
natural interleukin-2
References
- Butterworth AE (1984) Cell-mediated damage to helminths. Adv Parasitol 23:143–149 [DOI] [PubMed] [Google Scholar]
- Gleich GJ, Adolphson CR (1986) The eosinophilic leukocyte: structure and function. Adv Immunol 39:177–253 [DOI] [PubMed] [Google Scholar]
- Huland E, Huland H (1989) Local continuous high dose interleukin 2: a new therapeutic model for the treatment of advanced bladder carcinoma. Cancer Res 49:5469–5474 [PubMed] [Google Scholar]
- Jong EC, Klebanoff J (1980) Eosinophil-mediated mammalian tumor cell cytotoxycity: role of the peroxidase system. Immunology 124:1949–1953 [PubMed] [Google Scholar]
- Kolb E, Müller EM (1979) Local responses in primary and secondary human lung cancers: II. Clinical correlations. Br J Cancer 40:410–416 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowe D, Jorizzo J, Hutt MSR (1979) Tumor-associated eosinophilia: a review. J Clin Pathol 34:1343–1348 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ponzio NM, Speirs RS (1975) Lymphoid cell dependancy of eosinophil response to antigen. Immunology 28:243–251 [PMC free article] [PubMed] [Google Scholar]
- Silberstein DS, David JR (1987) The regulation of human eosinophhil function by cytokines. Immunol Today 8:380–385 [DOI] [PubMed] [Google Scholar]
- Silberstein DS, Schoof DD, Rodrick ML, Tai P-C, Spry CJF, David JR, Eberlein TJ (1989) Activation of eosinophils in cancer patients with IL-2 and IL-2-generated lymphokine-activated killer cells. J Immunol 142:2162–2167 [PubMed] [Google Scholar]
- Spry CJF (1985) Synthesis and secretion of eosinophil granule substances. Immunol Today 6:332–335 [DOI] [PubMed] [Google Scholar]
- Tai P-C, Spry CJF, Peterson C, Venge P, Olsson J (1984) Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein. Nature 309:182–184 [DOI] [PubMed] [Google Scholar]
- Tai P-C, Spry CJF, Olsen EGJ, Ackerman SJ, Dunnette S, Gleich GJ (1987) Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease. Lancet 1:643–647 [DOI] [PubMed] [Google Scholar]
- Walls RS, Basten A, Leuchars E, Davies AJS (1971) Mechanism for eosinophilic and neutrophilic leukocytoses. Br Med J 3:157–159 [DOI] [PMC free article] [PubMed] [Google Scholar]