Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Dec 1;168(6):2031–2043. doi: 10.1084/jem.168.6.2031

Interleukin 1-induced, T cell-mediated regression of immunogenic murine tumors. Requirement for an adequate level of already acquired host concomitant immunity

PMCID: PMC2189148  PMID: 3143799

Abstract

Intraperitoneal injection of human rIL-1 in a dose of 0.5 microgram daily for 5 d, or 1 microgram daily for 3 d, was capable of causing complete regression of immunogenic SA1 sarcoma growing subcutaneously in syngeneic or semisyngeneic mice. Higher doses of IL-1 were not more therapeutic against the SA1 sarcoma, but needed to be given to cause complete regression of the immunogenic L5178Y lymphoma. On the other hand, the P815 mastocytoma was much less responsive to IL-1 therapy, in that it failed to undergo complete regression in response to doses of IL-1 capable of causing regression of the L5178Y lymphoma. IL-1 caused regression of the SA1 sarcoma when given on days 6-8 of tumor growth, but not when given on days 1-3. This refractoriness of a small tumor to IL-1 therapy suggests that the antitumor action of IL-1 is based on an underlying host-immune response that is not generated until after day 3 of tumor growth. Direct evidence for the participation of host immunity in IL-1-induced tumor regression was supplied by results showing that IL-1 was not therapeutic against the SA1 sarcoma growing in T cell- deficient (TXB) mice, unless these mice were first infused with Ly-2+ and L3T4+ T cells from donor mice bearing an established SA1 sarcoma. In contrast, normal T cells, or T cells from donor mice bearing a YAC-1 lymphoma, failed to provide TXB recipients with the ability to cause regression of their SA-1 sarcoma in response to IL-1 treatment. The results are in keeping with the interpretation that exogenous IL-1, by augmenting the production of tumor-sensitized T cells, converts a subtherapeutic level of host immunity to a therapeutic level. The results suggest, in addition, that IL-1 only stimulates the replication of T cells that are already engaged in the antitumor immune response.

Full Text

The Full Text of this article is available as a PDF (690.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auron P. E., Webb A. C., Rosenwasser L. J., Mucci S. F., Rich A., Wolff S. M., Dinarello C. A. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907–7911. doi: 10.1073/pnas.81.24.7907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Digiacomo A., North R. J. Subtherapeutic numbers of tumour-sensitized, L3T4+, Ly 1+2- T cells are needed for endotoxin to cause regression of an established immunogenic tumour. Immunology. 1987 Mar;60(3):367–373. [PMC free article] [PubMed] [Google Scholar]
  3. Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
  4. Gaffney E. V., Tsai S. C. Lymphocyte-activating and growth-inhibitory activities for several sources of native and recombinant interleukin 1. Cancer Res. 1986 Aug;46(8):3834–3837. [PubMed] [Google Scholar]
  5. Havell E. A., Fiers W., North R. J. The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med. 1988 Mar 1;167(3):1067–1085. doi: 10.1084/jem.167.3.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Huang J. J., Newton R. C., Pezzella K., Covington M., Tamblyn T., Rutlege S. J., Gray J., Kelley M., Lin Y. High-level expression in Escherichia coli of a soluble and fully active recombinant interleukin-1 beta. Mol Biol Med. 1987 Jun;4(3):169–181. [PubMed] [Google Scholar]
  7. Lachman L. B., Dinarello C. A., Llansa N. D., Fidler I. J. Natural and recombinant human interleukin 1-beta is cytotoxic for human melanoma cells. J Immunol. 1986 Apr 15;136(8):3098–3102. [PubMed] [Google Scholar]
  8. Lomedico P. T., Gubler U., Hellmann C. P., Dukovich M., Giri J. G., Pan Y. C., Collier K., Semionow R., Chua A. O., Mizel S. B. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. 1984 Nov 29-Dec 5Nature. 312(5993):458–462. doi: 10.1038/312458a0. [DOI] [PubMed] [Google Scholar]
  9. Mannie M. D., Dinarello C. A., Paterson P. Y. Interleukin 1 and myelin basic protein synergistically augment adoptive transfer activity of lymphocytes mediating experimental autoimmune encephalomyelitis in Lewis rats. J Immunol. 1987 Jun 15;138(12):4229–4235. [PubMed] [Google Scholar]
  10. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  11. Nakamura S., Nakata K., Kashimoto S., Yoshida H., Yamada M. Antitumor effect of recombinant human interleukin 1 alpha against murine syngeneic tumors. Jpn J Cancer Res. 1986 Aug;77(8):767–773. [PubMed] [Google Scholar]
  12. Nawroth P. P., Bank I., Handley D., Cassimeris J., Chess L., Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. doi: 10.1084/jem.163.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. North R. J., Dye E. S. Ly 1+2- suppressor T cells down-regulate the generation of Ly 1-2+ effector T cells during progressive growth of the P815 mastocytoma. Immunology. 1985 Jan;54(1):47–56. [PMC free article] [PubMed] [Google Scholar]
  14. North R. J., Havell E. A. The antitumor function of tumor necrosis factor (TNF) II. Analysis of the role of endogenous TNF in endotoxin-induced hemorrhagic necrosis and regression of an established sarcoma. J Exp Med. 1988 Mar 1;167(3):1086–1099. doi: 10.1084/jem.167.3.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. North R. J. Models of adoptive T-cell-mediated regression of established tumors. Contemp Top Immunobiol. 1984;13:243–257. doi: 10.1007/978-1-4757-1445-6_12. [DOI] [PubMed] [Google Scholar]
  16. North R. J. Radiation-induced, immunologically mediated regression of an established tumor as an example of successful therapeutic immunomanipulation. Preferential elimination of suppressor T cells allows sustained production of effector T cells. J Exp Med. 1986 Nov 1;164(5):1652–1666. doi: 10.1084/jem.164.5.1652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. North R. J. The therapeutic significance of concomitant antitumor immunity. I. LY-1-2+ T cells from mice with a progressive tumor can cause regression of an established tumor in gamma-irradiated recipients. Cancer Immunol Immunother. 1984;18(2):69–74. doi: 10.1007/BF00205736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Onozaki K., Matsushima K., Aggarwal B. B., Oppenheim J. J. Human interleukin 1 is a cytocidal factor for several tumor cell lines. J Immunol. 1985 Dec;135(6):3962–3968. [PubMed] [Google Scholar]
  19. Stern D. M., Bank I., Nawroth P. P., Cassimeris J., Kisiel W., Fenton J. W., 2nd, Dinarello C., Chess L., Jaffe E. A. Self-regulation of procoagulant events on the endothelial cell surface. J Exp Med. 1985 Oct 1;162(4):1223–1235. doi: 10.1084/jem.162.4.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES