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Histological analysis of IL-2 induced regression of murine solid SL2-tumors

  • Research Articles
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Biotherapy

Abstract

When DBA/2 mice are inoculated both intraperitoneally (i.p.) and subcutaneously (s.c.) with syngeneic SL2 lymphoma cells and treated i.p. on day 10–14 with 20,000 units IL-2/day, about 50% of the mice reject both the ascitic tumour and the s.c. tumour. During IL-2 therapy large areas of necrosis appear in the solid SL2 tumours between day 12 and 15. Immunohistochemical studies show that only a small number of infiltrating cells is present in the tumours. The percentage of macrophages (MHC-II+)in the tumours is about 1 and the percentage of T-lymphocytes (αβ-TCR+) about 0.5. No differences in the numbers of infiltrating cells are seen in untreated and IL-2 treated tumour bearing mice. The tumoursurrounding infiltrate consists mainly of mononuclear cells: about 50% macrophages, 20% CD8+ cells, and 15% CD4+ cells. No tumour-infiltrating cells were found that express the IL-2 receptor.

We conclude that direct cytotoxic activity of tumour infiltrating cells cannot account for the rapid occurrence of necrosis.

When L3T4+ cells were eliminated by treating the mice withα-L3T4 monoclonal antibodies before tumor inoculation and treatment with rIL-2, tumor eradication did not occur. So, L3T4+ helper T-cells are essential for IL-2-mediated tumour regression. Exogenous rIL-2 is not directly responsible for the induced tumour regression. A significant stagnation of intratumoural bloodflow is observed after histological analysis; yet it still needs to be determined whether this is the primary cause or consequence of the observed necrosis.

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Abbreviations

BSA:

bovine serum albumin

CTL:

cytotoxic T-lymphocyte

FACS:

fluorescence activated cell sorter

HE:

haematoxylin and eosin

IFN:

interferon

IL-2:

interleukin-2

IL-2R:

interleukin-2 receptor

i.p.:

intraperitoneal(ly)

i.V.:

intravenous(ly)

LAK:

lymphokine-activated killer

MHC:

major histocompatibility complex

PBS:

phosphate buffered saline

s.c.:

subcutaneous(ly)

TCR:

T-cell receptor

TNF:

tumour necrosis factor

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Authors and Affiliations

  1. Department of Pathology, University Hospital Utrecht, H 04.312, P.O. Box 85500, 3508, GA Utrecht, The Netherlands

    Riks A. Maas, Hub F. J. Dullens, D. Henk, J. Van Weering, Hanneke J. I. De Mik, Jan -Willem Koten, R. J. Belger & Willem Den Otter

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  1. Riks A. Maas
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  2. Hub F. J. Dullens
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  3. D. Henk
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  4. J. Van Weering
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  5. Hanneke J. I. De Mik
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  6. Jan -Willem Koten
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  7. R. J. Belger
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  8. Willem Den Otter
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Maas, R.A., Dullens, H.F.J., Henk, D. et al. Histological analysis of IL-2 induced regression of murine solid SL2-tumors. Biotherapy 6, 83–91 (1993). https://doi.org/10.1007/BF01877421

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  • DOI: https://doi.org/10.1007/BF01877421

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