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. 1991 Aug;64(2):239–242. doi: 10.1038/bjc.1991.283

Perforin expression in lymphocytes infiltrated to human colorectal cancer.

H Nakanishi 1, T Monden 1, H Morimoto 1, T Kobayashi 1, T Shimano 1, T Mori 1
PMCID: PMC1977537  PMID: 1892750

Abstract

Perforin (PFP) is a cytotoxic protein released from killer cells. PFP immunoreactivity in human peripheral blood lymphocytes (PBL) and tumour infiltrating lymphocytes (TIL) was investigated immunocytochemically with the aid of an anti-PFP monoclonal antibody. PFP was detected in the cytoplasm of 10% of PBL. We performed a double staining of PFP+ cells with Leu11b/CD16, Leu2a/CD8, or Leu3a/CD4 and showed that PFP was produced by 9% of CD8+ cells and 18% of CD16+ cells but not by CD4+ cells. In 28 colorectal cancer tissues, PFP immunoreactivity was observed in the lymphocytes infiltrating to the tumour stroma. The PFP+ cells were most numerous in Dukes A and decreased in number according to the progression of tumours. The PFP+ cells in TIL exhibited the same phenotypes as those in PBL but the PFP+ cells were more numerous in CD8+ cells than in CD16+ cells at all stages. This study represents the first evidence that PFP is mainly secreted from CD8+ cells in tumour tissues. It is hypothesised that the decrease in the number of PFP+ cells in accordance with tumour progression may reflect the suppression of the hosts local immunity.

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Selected References

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

  1. Henkart P. A. Mechanism of lymphocyte-mediated cytotoxicity. Annu Rev Immunol. 1985;3:31–58. doi: 10.1146/annurev.iy.03.040185.000335. [DOI] [PubMed] [Google Scholar]
  2. Lanier L. L., Le A. M., Civin C. I., Loken M. R., Phillips J. H. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed] [Google Scholar]
  3. Lanier L. L., Le A. M., Phillips J. H., Warner N. L., Babcock G. F. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol. 1983 Oct;131(4):1789–1796. [PubMed] [Google Scholar]
  4. Lichtenheld M. G., Olsen K. J., Lu P., Lowrey D. M., Hameed A., Hengartner H., Podack E. R. Structure and function of human perforin. Nature. 1988 Sep 29;335(6189):448–451. doi: 10.1038/335448a0. [DOI] [PubMed] [Google Scholar]
  5. Lichtenheld M. G., Podack E. R. Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences. J Immunol. 1989 Dec 15;143(12):4267–4274. [PubMed] [Google Scholar]
  6. Lowrey D. M., Aebischer T., Olsen K., Lichtenheld M., Rupp F., Hengartner H., Podack E. R. Cloning, analysis, and expression of murine perforin 1 cDNA, a component of cytolytic T-cell granules with homology to complement component C9. Proc Natl Acad Sci U S A. 1989 Jan;86(1):247–251. doi: 10.1073/pnas.86.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Masson D., Tschopp J. Isolation of a lytic, pore-forming protein (perforin) from cytolytic T-lymphocytes. J Biol Chem. 1985 Aug 5;260(16):9069–9072. [PubMed] [Google Scholar]
  8. Podack E. R., Young J. D., Cohn Z. A. Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8629–8633. doi: 10.1073/pnas.82.24.8629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rabinowich H., Steiner Z., Klajman A. Clonal analysis of human tumor infiltrating lymphocytes reactive with autologous tumor cells: different target cell specificities of NK-like and cytotoxic T-cell clones. Cell Immunol. 1987 Feb;104(2):210–217. doi: 10.1016/0008-8749(87)90023-2. [DOI] [PubMed] [Google Scholar]
  10. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Shimokawara I., Imamura M., Yamanaka N., Ishii Y., Kikuchi K. Identification of lymphocyte subpopulations in human breast cancer tissue and its significance: an immunoperoxidase study with anti-human T- and B-cell sera. Cancer. 1982 Apr 1;49(7):1456–1464. doi: 10.1002/1097-0142(19820401)49:7<1456::aid-cncr2820490724>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  12. Shinkai Y., Ishikawa H., Hattori M., Okumura K. Resistance of mouse cytolytic cells to pore-forming protein-mediated cytolysis. Eur J Immunol. 1988 Jan;18(1):29–33. doi: 10.1002/eji.1830180106. [DOI] [PubMed] [Google Scholar]
  13. Shinkai Y., Takio K., Okumura K. Homology of perforin to the ninth component of complement (C9). Nature. 1988 Aug 11;334(6182):525–527. doi: 10.1038/334525a0. [DOI] [PubMed] [Google Scholar]
  14. Tschopp J., Jongeneel C. V. Cytotoxic T lymphocyte mediated cytolysis. Biochemistry. 1988 Apr 19;27(8):2641–2646. doi: 10.1021/bi00408a001. [DOI] [PubMed] [Google Scholar]
  15. Werkmeister J. A., Pihl E., Nind A. P., Flannery G. R., Nairn R. C. Immunoreactivity by intrinsic lymphoid cells in colorectal carcinoma. Br J Cancer. 1979 Dec;40(6):839–847. doi: 10.1038/bjc.1979.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Young J. D., Cohn Z. A. Cellular and humoral mechanisms of cytotoxicity: structural and functional analogies. Adv Immunol. 1987;41:269–332. doi: 10.1016/s0065-2776(08)60033-4. [DOI] [PubMed] [Google Scholar]
  17. Young J. D., Cohn Z. A., Podack E. R. The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities. Science. 1986 Jul 11;233(4760):184–190. doi: 10.1126/science.2425429. [DOI] [PubMed] [Google Scholar]
  18. Young J. D., Hengartner H., Podack E. R., Cohn Z. A. Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell. 1986 Mar 28;44(6):849–859. doi: 10.1016/0092-8674(86)90007-3. [DOI] [PubMed] [Google Scholar]
  19. Young L. H., Foster C. S., Young J. D. In vivo expression of perforin by natural killer cells during a viral infection. Studies on uveitis produced by herpes simplex virus type I. Am J Pathol. 1990 May;136(5):1021–1030. [PMC free article] [PubMed] [Google Scholar]
  20. Young L. H., Klavinskis L. S., Oldstone M. B., Young J. D. In vivo expression of perforin by CD8+ lymphocytes during an acute viral infection. J Exp Med. 1989 Jun 1;169(6):2159–2171. doi: 10.1084/jem.169.6.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zalman L. S., Brothers M. A., Chiu F. J., Müller-Eberhard H. J. Mechanism of cytotoxicity of human large granular lymphocytes: relationship of the cytotoxic lymphocyte protein to the ninth component (C9) of human complement. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5262–5266. doi: 10.1073/pnas.83.14.5262. [DOI] [PMC free article] [PubMed] [Google Scholar]

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