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Locoregional therapy with polyethylene-glycol-modified interleukin-2 of an intradermally growing hepatocellular carcinoma in the guinea pig induces T-cell-mediated antitumor activity

  • Original Articles
  • Interleukin-2, Polyethylene-Glycol, Locoregional Immunotherapy, Guinea Pig Hepatoma
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Therapy with repeated intratumoral and perilymphatic administration of relatively low doses of polyethylene-glycol(PEG)-modified interleukin-2 (IL-2) in the syngeneic guinea pig line 10 (L10) hepatocarcinoma results in significant local tumor growth inhibition and a delay in development of regional lymph node metastases of more than 3 weeks when compared to controls. Occasionally animals are cured of tumor. The mechanism of this antitumor activity was studied. The antitumor activity of locoregionally administered PEG-IL-2 was abrogated by pretreatment with polyclonal anti-thymocyte serum, indicating that the observed tumor growth inhibition was a T-cell-mediated phenomenon. Besides the locoregional tumor growth inhibition, a systemic effect was recorded as the growth of a second tumor cell inoculum at the contralateral side was inhibited as well. Furthermore, those animals cured after PEG-IL-2 therapy developed specific immunity against the L10 tumor and this immunity could be transferred to naive animals by spleen cells. Immunohistological observations of the tumor site revealed a slight increase of helper and cytotoxic T cell subpopulations after PEG-IL-2 therapy. More pronounced, however, was the rise in number of eosinophilic granulocytes present in the stroma surrounding the tumor cells. Involvement of cytotoxic cells in the antitumor effects of PEG-IL-2 could not be demonstrated: regional lymph node cells and spleen cells obtained immediately after therapy (day 15) or on day 21 showed no cytotoxic activity in vitro against L10, K562, Daudi and line 1 (L1) target cells.

In conclusion, locoregional therapy with PEG-IL-2 induced a systemic T-cell-mediated antitumor response. As no cytotoxic T cell activity was measured, however, the underlying mechanism is most likely a T-helper response. Eosinophils at the tumor site may be tumoricidal but further experiments must reveal the role of these cells in the PEG-IL-2-induced tumor regression.

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Authors and Affiliations

  1. Laboratory for Pathology, National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

    L. T. M. Balemans, P. A. Steerenberg, B. E. M. Van Driel & W. Den Otter

  2. Department of Medicine, Division of Medical Oncology, University Hospital, Nijmegen, The Netherlands

    V. Mattijssen & P. H. M. De Mulder

  3. Department of Pathology, University Hospital, Utrecht, The Netherlands

    L. T. M. Balemans & W. Den Otter

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  1. L. T. M. Balemans
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  2. V. Mattijssen
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  3. P. A. Steerenberg
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  4. B. E. M. Van Driel
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  5. P. H. M. De Mulder
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Balemans, L.T.M., Mattijssen, V., Steerenberg, P.A. et al. Locoregional therapy with polyethylene-glycol-modified interleukin-2 of an intradermally growing hepatocellular carcinoma in the guinea pig induces T-cell-mediated antitumor activity. Cancer Immunol Immunother 37, 7–14 (1993). https://doi.org/10.1007/BF01516936

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  • DOI: https://doi.org/10.1007/BF01516936

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