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Toxicologic Pathology
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Infiltrating CD8+ T Lymphocytes, Natural Killer Cells, and Expression of IL-10 and TGF-β1 in Chemically Induced Neoplasms in Male Wistar Rats

Ana Lúcia Tozzi Spinardi-Barbisan

Departamento de Patologia, TOXICAN, Faculdade de Medicina, UNESP, Botucatu, 18618-000, SP, Brazil

Luís Fernando Barbisan

Departamento de Morfologia, Instituto de Biociências, UNESP, Botucatu, 18618-000, SP, Brazil

João Lauro Viana De Camargo

Departamento de Patologia, TOXICAN, Faculdade de Medicina, UNESP, Botucatu, 18618-000, SP, Brazil

Maria Aparecida Marchesan Rodrigues

Departamento de Patologia, TOXICAN, Faculdade de Medicina, UNESP, Botucatu, 18618-000, SP, Brazil, mariar{at}fmb.unesp.br

The present study aimed to estimate the number of CD8+ T and natural killer (NK) infiltrating cells and the expression of interleukin-10 (IL-10) and transforming growth factor beta 1 (TGF-β1) in chemically induced neoplasms in an initiation-promotion bioassay for carcinogenesis. Male Wistar rats were treated withN-nitrosodiethylamine, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, dihydroxy-di-N-propylnitrosamine, and 1,2-dimethylhydrazine for 4 weeks. Two groups were subsequently exposed through diet to phenobarbital (0.05%) or 2-acetylaminofluorene (0.01%) for 25 weeks. An untreated group was used as a control. Immune cells and cytokines were immunohistochemically evaluated in neoplasms and in surrounding normal tissues at the liver, kidneys, lung, and small and large intestines. When compared to the respective normal tissues, an increased number of NK cells was verified infiltrating the colon, lung, and kidney neoplasms, while the number of CD8+ T cells decreased in the intestine and lung neoplasms. Expression of IL-10 was found mainly in kidney tumors. TGF-β1 was expressed mainly in the liver and kidneys tumors. The results indicate that the differential occurrence of immune cells between neoplastic and normal tissues could be dependent upon tumor microenvironment.

Key Words: Initiation-promotion • neoplasia • cytokines • tumor-infiltrating lymphocytes • natural killer cells.

References

  • Afshari, C.A., and Barrett J.C. (1993). Cell cycle controls: potential targets for chemical carcinogens? Environ Health Perspect 101, 9—14.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Anderson, J.A., Lentsch, A.B., Hadjiminas, D.J., Miller, F.N., Martin, A.W., Nakagawa, K., and Edwards, M.J. (1996). The role of cytokines, adhesion molecules, and chemokines in interleukin-2 induced lymphocytic infiltration in C57BL/6 mice. J Clin Invest 97, 1952—9.[Web of Science][Medline] [Order article via Infotrieve]
  • Asselin-Paturel, C.A., Echchakir, H., Carayol, G., Gay, F., Opolon, P., Grunenwald, D., Chouaib, S., and Chouaib, F.M. (1998). Quantitative analysis of Th1, Th2 and TGF-β cytokine expression in tumor, TIL and PBL of non-small cell lung cancer patients. Int J Cancer 77, 7—12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Beckstead, J.H. (1994). A simple technique for preservation on fixation-sensitive antigens in paraffin-embedded tissues. J Histochem Cytochem 8, 1127—34.
  • Blay, J.Y., Burdin, N., Rousset, F., Lenoir, G., Biro, P., Philip, T., Banchereau, J., and Facrot, M.C. (1993). Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor. Blood 82, 2169—74.[Abstract/Free Full Text]
  • Chouaib, S., Asselin-Paturel, C., Mami-Chouaib, F., Caignard, A., and Blay, J.Y. (1997). The tumor-host immune system conflict: from tolerance and resistance to destruction. Immunol Today 18, 493—7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Coca, S., Piqueras, J.P., Martinez, D., Colmenarejo, A., Saez, M.A., Vallejo, C., Martos, J.A., and Moreno, M. (1997). The prognostic significance of intramural natural killer cells in patients with colorectal carcinoma. Cancer 79, 2320—8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • de Wall-Malefyt, R., Yssel, H., and Vries, J.E. (1993). Direct effect of IL-10 on subsets of human CD4+ T cells clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol 150, 4754— 65.[Abstract]
  • Filgueira, L., Zuber, M., Merlo, A., Caetano, V., Schultz, E., Harder, F., Spagnoli, G.C., and Hebere, M. (1993). Cytokine gene transcription in renal cell carcinoma. Br J Surg 80, 1322—5.[Web of Science][Medline] [Order article via Infotrieve]
  • Houbiers, J. G. A, Nijman, H.W., Van Der Burg, S.H., Drijfhout, J.W., Kenemans, P., Van De Velde, C.J., Brand, A., Momburg, F., Kast, W.M., and Melief, C.J. (1993). In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild type p53. Eur J Immunol 23, 2072—7.[Web of Science][Medline] [Order article via Infotrieve]
  • Hsu, S.M., Raine, L., and Fanger, N. (1981). Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29, 577—80.[Abstract]
  • Iarc. (1990). Tumors of the auditory sebaceous glands. In Pathology of Tumours in Laboratory Animals (V. S. Turusov and U. Mohr, eds.), pp. 1— 390. International Agency for Research on Cancer, Scientific Publications, Lyon, France.
  • Iarc. (1999). Shirai, T., Hirose, M., and Ito, N. Medium-term bioassay in rats forrapid detection of the carcinogenic potential of chemicals. In The Use of Short-Term and Medium-Term Tests for Carcinogens and Data on Genetic Effects in Carcinogenic Hazard Evaluation (D. B. McGregor, J. M. Rice, and S. Venitt, eds.), pp. 251—272. International Agency for Research on Cancer, Lyon, France.
  • Ito, N., Imaida, K., Hirose, M., and Shirai, T. (1998). Medium-term bioassays for carcinogenicity of chemical mixtures. Environ Health Perspect 106, 1331—6.[Web of Science][Medline] [Order article via Infotrieve]
  • Ito, N., Shirai, T., and Hasegawa, R. (1992). Medium-Term Bioassays for Carcinogens. In Mechanisms of Carcinogenesis in Risk Identification (H. Vainio, P. N. Magee, D. B. McGregor, A. J. McMichael, eds.), Vol. 116, pp. 356—88, IARC Scientific Publications, Lyon, France.
  • Kaklamanis L., Townsend A., Doussis-Anagnostopoulou I.A., Mortensen N., Harris A.L., and Gatter K.C. (1994). Loss of major histocompatibility complex-encoded transporter associated with antigen presentation (TAP) in colorectal cancer. Am J Pathol 145, 505—9.[Abstract]
  • Marrogi A.J., Munshi A., Merogi A.J., Ohadike Y., and El-Habashi A. (1997). Study of tumor infiltrating lymphocytes and transforming growth factor-β as prognostic factors in breast carcinoma. Int J Cancer 74, 492— 501.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Massague, J. (1998). TGF-beta signal transduction [Review]. Annu Rev Biochem 67, 753—91.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ménétrier-Caux, C., Bain, C., Favrot, M.C., Duc, A., and Blay, J.Y. (1999). Renal cell carcinoma induces interleukin 10 and prostaglandin E2 production by monocytes. Br J Cancer 79, 119—30.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Merogi, A.J., Marrogi, A.J., Ramesh, R., Robinson, W.R., Fermin, C.D., and Freeman, S.M. (1997). Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas. Human Pathol 28, 321—31.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mossman, T.R. (1994). Properties and functions of interleukin-10. Adv Immunol 56, 1—26.[Web of Science][Medline] [Order article via Infotrieve]
  • Naito, Y., Saito, K., Shiiba, K., Ohuchi, A., Saigenji, K., Nagura, H., and Ohtani, H. (1998). CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58, 3491—4.[Abstract/Free Full Text]
  • Nakagomi, H., Pisa, P., Pisa, E.K., Yamamoto, Y., Halapi, E., Backlin, K., Juhlin, C., and Kiessling, R. (1995). Lack of interleukin-2 (IL-2) expression and selective expression of IL-10 mRNA in human renal cell carcinoma. Int J Cancer 63, 366—71.[Web of Science][Medline] [Order article via Infotrieve]
  • O'Hara, R.J., Greenman, J., Macdonald, A.W., Gaskell, K.M., Topping, K.P., Duthie, G.S., Kerin, M.J., Lee, P.W.R., and Monson, J.R.T. (1998). Advanced colorectal cancer is associated with impaired interleukin 12 and interleukin 10 production. Clin Cancer Res 4, 1943—8.[Abstract]
  • Ohno, S., Tachibana, M., Fujii, T., Ueda, S., Kubota, H., and Nagasue, N. (2002). Role of stromal collagen in immunomodulation and prognosis of advanced gastric carcinoma. Int J Cancer 97, 770—4.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Park, D.Y., Hwang, S.Y., and Suh, K.S. (2001). Expression of transforming growth factor TGF-β1 and TGF-β type II receptor in preneoplastic lesions during chemical hepatocarcinogenesis of rats. Toxicol Pathol 29, 541—9.[Abstract/Free Full Text]
  • Pasche, B. (2001). Role of transforming growth factor beta in cancer. J Cell Physiol 186, 153—68.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Pisa, P., Halapi, E., Pisa, E.K., Gerdin, E., Hising, C., Bucht, A., and Kiessling, R. (1992). Selective expression of interleukin-10, interferon-{gamma}, and granulocity macrophage colony stimulating factor in ovarian cancer biopsies. Proc Natl Acad Sci USA 89, 7708—12.[Abstract/Free Full Text]
  • Pretolani, M., Stordeur, P., and Goldman, M. (1999). Interleukin 10. Cytokines in cancer. In The Cytokine Network and Immune Functions (J. Thèze, ed.), pp. 45—9. Oxford University Press, London, U.K.
  • Ropponen, K.M., Eskelinen, M.J., Lipponen, P.K., Alhava, E., and Kosma, V. (1997). Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer. J Pathol 182, 318—24.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Seung, L.P., Rowley, D.A., and Schreiber, H. (1999). Cytokines in cancer. In The Cytokine Network and Immune Functions (J. Thèze, ed.), pp. 335—45. Oxford University Press, London, U.K.
  • Smyth, M.J., Strobl, S.L., Young, H.A., Ortaldo, J.R., and Ochoa, A.C. (1991). Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta. J Immunol 146, 3289—97.[Abstract]
  • Spinardi, A.L.T., Kaneno, R., Rodrigues, M.A.M., Salvadori, D.M.F., Rocha, N., Barbisan, L.F., Ribeiro, L.R., and de Camargo, J.L.V. (1999). Natural killer activity in a medium-term multi-organ bioassay for carcinogenesis. Jpn J Cancer Res 90, 101—7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Spinardi-Barbisan, A.L.T., Kaneno, R., Rodrigues, M.A.M., Salvadori, D.M.F., Moreira, E.L.T., Barbisan, L.F., and de Camargo, J.L.V. (2000). Lymphoproliferative response and T lymphocyte subsets in a medium-term multi-organ bioassay for carcinogenesis in Wistar rats. Cancer Lett 154, 121—9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Spinardi-Barbisan, A.L.T., Kaneno, R., Barbisan, L.F., de Camargo, J.L.V., and Rodrigues, M.A.M. (2004). Chemically induced immunotoxicity in a medium-term multiorgan bioassay for carcinogenesis with Wistar rats. Toxicol Appl Pharmacol 194, 132—40.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Taga, K., Mostowski, H., and Tosato, G. (1993). Human interleukin-10 can directly inhibit T cell growth. Blood 81, 2964—71.[Abstract/Free Full Text]
  • Takahashi, S., Hasegawa, R., Masui, T., Misoguchi, M., Fukushima, S., and Ito, N. (1992). Establishment of multi-organ carcinogenesis bioassay using rats treated with a combination of five different carcinogens. J Toxicol Pathol 5, 151—6.
  • Tlsty, T.D. (2001). Stromal cells can contribute oncogenic signals. Cancer Biol 11, 97—104.[CrossRef]
  • Wang, Q., Redovan, C., Tubbs, R., Olencki, T., Klein, E., Kudoh, S., Finke, J., and Bukowski, R.M. (1995). Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor infiltrating lymphocytes. Int J Cancer 61, 780—5.[Web of Science][Medline] [Order article via Infotrieve]
  • Wong, P.Y., Staren, E.D., Natasha Tereshkova, M.S., and Braun, D.P. (1998). Functional analysis of tumor-infiltrating leukocytes in breast cancer patients. J Surg Res 76, 95—103.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 32, No. 5, 548-557 (2004)
DOI: 10.1080/01926230490505059
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