Abstract
It was shown that although intravenous administration of bacterial endotoxin caused extensive hemorrhagic necrosis of four different syngeneic murine tumors, only two of these tumors subsequently underwent complete regression: the two that were shown to be immunogeneic as classically defined. An immunologic basis for endotoxin- induced regression was further indicated by the additional findings that regression, but not hemorrhagic necrosis, of the two immunogenic tumors failed to occur in mice that were immunodepressed by whole-body gamma-irradiation, or that were made T-cell deficient by thymectomy and irradiation. That endotoxin-induced regression is T-cell mediated was suggested by the findings that tumor regression was followed by a state of long-lived immunity to a tumor cell challenge implant, and with the possession by the host of T cells that were capable of passively transferring this state of immunity to normal recipients. It is concluded that although parenteral injection of endotoxin causes hemorrhagic necrosis of most solid murine tumors, it is only those tumors that are immunogenic enough to evoke the generation of T-cell- mediated immunity which subsequently go on to completely regress.
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Selected References
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- Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen A., Schlesinger M. Absorption of guinea pig serum with agar. A method for elimination of itscytotoxicity for murine thymus cells. Transplantation. 1970 Jul;10(1):130–132. doi: 10.1097/00007890-197007000-00027. [DOI] [PubMed] [Google Scholar]
- Coley W. B. II. Contribution to the Knowledge of Sarcoma. Ann Surg. 1891 Sep;14(3):199–220. doi: 10.1097/00000658-189112000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green S., Dobrjansky A., Carswell E. A., Kassel R. L., Old L. J., Fiore N., Schwartz M. K. Partial purification of a serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1976 Feb;73(2):381–385. doi: 10.1073/pnas.73.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green S., Dobrjansky A., Chiasson M. A., Carswell E., Schwartz M. K., Old L. J. Corynebacterium parvum as the priming agent in the production of tumor necrosis factor in the mouse. J Natl Cancer Inst. 1977 Nov;59(5):1519–1522. doi: 10.1093/jnci/59.5.1519. [DOI] [PubMed] [Google Scholar]
- Hoffmann M. K., Oettgen H. F., Old L. J., Mittler R. S., Hammerling U. Induction and immunological properties of tumor necrosis factor. J Reticuloendothel Soc. 1978 Apr;23(4):307–319. [PubMed] [Google Scholar]
- North R. J. Importance of thymus-derived lymphocytes in cell-mediated immunity to infection. Cell Immunol. 1973 Apr;7(1):166–176. doi: 10.1016/0008-8749(73)90193-7. [DOI] [PubMed] [Google Scholar]
- North R. J., Kirstein D. P. T-cell-mediated concomitant immunity to syngeneic tumors. I. Activated macrophages as the expressors of nonspecific immunity to unrelated tumors and bacterial parasites. J Exp Med. 1977 Feb 1;145(2):275–292. doi: 10.1084/jem.145.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parr I., Wheeler E., Alexander P. Similarities of the anti-tumour actions of endotoxin, lipid A and double-stranded RNA. Br J Cancer. 1973 May;27(5):370–389. doi: 10.1038/bjc.1973.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Russell S. W., Doe W. F., Hoskins R. G., Cochrane C. G. Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent inflammatory cells. Int J Cancer. 1976 Sep 15;18(3):322–330. doi: 10.1002/ijc.2910180309. [DOI] [PubMed] [Google Scholar]
- Wepsic H. T., Kronman B. S., Zbar B., Borsos T., Rapp H. J. Immunotherapy of an intramuscular tumor in strain-2 guinea pigs: prevention of tumor growth by intradermal immunization and by systemic transfer of tumor immunity. J Natl Cancer Inst. 1970 Aug;45(2):377–386. [PubMed] [Google Scholar]