Abstract
Several immunological in vitro tests were performed on peripheral blood mononuclear cells of patients with adenocarcinoma of the prostate, stages A, B, C, D. The cytotoxicity of effector natural killer cells towards K-562 targets decreased with increasing disease spread, while their percentage was not significantly changed. The proportion of CD4 (helper/inducer) cells tended to fall with tumor advance, but the proportion of CD8 (suppressor/cytotoxic) cells remained almost constant. Secretion of interleukin-2 from peripheral blood mononuclear cells was diminished with disease progression. Pretreatment of a patient's lymphocytes with cimetidine (antagonist of H-2-bearing suppressor T cells) or indomethacin (inhibitor of prostaglandin synthesis) enhanced natural killer activity.
Our data point to the existence of abberant immune functions in early stages of carcinoma of the prostate and to aggravation of these immune abnormalities in advanced disease.
Keywords: Adenocarcinoma, Natural Killer, Prostaglandin, Natural Killer Cell, Peripheral Blood Mononuclear Cell
References
- 1.Allavena P, Introna M, Mangioni C, Mantovani A. Inhibition of NK activity by tumor associated lymphoid cells from ascitic ovarian carcinomas. J Natl Cancer Inst. 1981;67:379. [PubMed] [Google Scholar]
- 2.Balch CM, Dougherty PA, Tilden AB. Executive prostaglandin E2 production by suppressor monocytes in head and neck cancer patients. Ann Surg. 1982;196:645. doi: 10.1097/00000658-198212001-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Bankhurst AD. The modulation of human NK cell activity by prostaglandins. J Clin Lab Immunol. 1982;7:85. [PubMed] [Google Scholar]
- 4.Barlozzari T, Reynolds CW, Herberman RB. In vivo role of natural killer cells: involvement of large granular lymphocytes in the clearance of tumor cells in antiasialo GM1-treated rats. J Immunol. 1983;131:1024. [PubMed] [Google Scholar]
- 5.Böyum A. Separation of leucocytes from blood and bone marrow. Scand J Clin Invest 21. 1968;97:77. [PubMed] [Google Scholar]
- 6.Braun DP, Harris JE. Relationship of leucocyte numbers, immunoregulatory cell function and PHA responsiveness in cancer patients. J Natl Cancer Inst. 1981;67:809. [PubMed] [Google Scholar]
- 7.Braun DP, Harris JE, Rubinstein M. Relationship of arachidonic acid metabolism in indomethacin sensitive immunoregulatory function and lymphocyte PGE sensitivity in PBMC of disseminated solid tumor cancer patients. J Immunopharmacol. 1984;6:227. doi: 10.3109/08923978409019463. [DOI] [PubMed] [Google Scholar]
- 8.De Baer KP, Braun DP, Harris JE. Natural cytotoxicity and antibody dependent cytotoxicity in solid tumor cancer patients. Regulation by adherent cells. Clin Immunol Immunopathol. 1982;23:133. doi: 10.1016/0090-1229(82)90078-2. [DOI] [PubMed] [Google Scholar]
- 9.Domzig W, Stadler BM, Herberman RB. Interleukin-2 dependence of human NK cell activity. J Immunol. 1983;130:1970. [PubMed] [Google Scholar]
- 10.Flodgren P, Sjogren O. Influence in vitro on NK and K cell activities by cimetidine and indomethacin with and without simultaneous exposure to interferon. Cancer Immunol Immunother. 1985;19:28. doi: 10.1007/BF00199308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Flodgren P, Bongstrom S, Jansson P, Lindstrom C, Sjogren HO. Metastatic malignant melanoma: regression induced by combined treatment with interferon HUIFN-α (αe) and cimetidine. Int J Cancer. 1983;32:657. doi: 10.1002/ijc.2910320603. [DOI] [PubMed] [Google Scholar]
- 12.Gerson JM, Varesio L, Herberman RB. Systemic and in situ NK activities in mice bearing progressively growing murine sarcoma virus induced tumors. Int J Cancer. 1981;27:243. doi: 10.1002/ijc.2910270218. [DOI] [PubMed] [Google Scholar]
- 13.Gillis S, Feanin M, Ou W, Smith KA. T cell growth: parameters of production and quantitative microassay for activity. J Immunol. 1980;120:2027. [PubMed] [Google Scholar]
- 14.Goodwin JS, Messner RP, Peake GT. Prostaglandin suppression of mitogen stimulated dependent restoration of local graft versus host reaction among cells from cancer patients. J Natl Cancer Inst. 1980;65:317. [PubMed] [Google Scholar]
- 15.Haller O, Hannson M, Kiessling R, Wigzell H. Nonconventional NK cells may play a decisive role in providing resistance against syngeneic tumor cells in vivo. Nature. 1977;270:609. doi: 10.1038/270609a0. [DOI] [PubMed] [Google Scholar]
- 16.Han T, Takita H. Indomethacin mediated enhancement of lymphocyte response to mitogens in healthy subjects and lung cancer patients. Cancer. 1980;46:2416. doi: 10.1002/1097-0142(19801201)46:11<2416::aid-cncr2820461120>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
- 17.Harris JE, DeBaer KP, Vahey AL, et al. The measurement of leucocyte subsets in the peripheral blood of cancer patients with solid tumors using monoclonal antibody regents. Med Pediat Oncol. 1982;10:185. doi: 10.1002/mpo.2950100214. [DOI] [PubMed] [Google Scholar]
- 18.Herberman RB, Munn ME, Lavnin DH. Natural cytotoxicity activity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer. 1975;16:216. doi: 10.1002/ijc.2910160204. [DOI] [PubMed] [Google Scholar]
- 19.Herr HW. Suppressor cells in immunodepressed bladder and prostate cancer patients. J Urol. 1980;123:635. [PubMed] [Google Scholar]
- 20.Herr HW. Adherent suppressor cells in the blood of patients with bladder cancer. J Urol. 1981;126:457. doi: 10.1016/s0022-5347(17)54574-7. [DOI] [PubMed] [Google Scholar]
- 21.Hinai U, Hill NO, Motoo Y, Osther K. Cimetidine enhances interferon induced augmentation of NK cell activity and suppresses interferon production. Acta Pathol Microbiol Immunol Scand. 1985;93:153. doi: 10.1111/j.1699-0463.1985.tb02938.x. [DOI] [PubMed] [Google Scholar]
- 22.Jewett NJ. The present status of radical prostatectomy for stages A and B prostatic cancer. Urol Clin North Am. 1975;2:105. [PubMed] [Google Scholar]
- 23.Karavodin LM, Giuliano AE, Golub SH. T lymphocyte subsets in patients with malignant melanoma. Cancer Immunol Immunother. 1981;11:251. [Google Scholar]
- 24.Kasai JC, Leclerc JC, McVay-Bodreau L, Shen FW, Cantor H. Direct evidence that NK cells in non immune spleen cell populations prevent tumor growth in vivo. J Exp Med. 1979;149:1260. doi: 10.1084/jem.149.5.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Lang NP, Ortaldo JR, Bonnard GP, Herberman RB. Interferon and prostaglandins: effects on human natural and lectin induced cytotoxicity. J Natl Cancer Inst. 1982;69:339. [PubMed] [Google Scholar]
- 26.Miyaska N, Darnell B, Baron S, Talal N. Interleukin-2 enhances natural killing of normal lymphocytes. Cell Immunol. 1984;84:154. doi: 10.1016/0008-8749(84)90086-8. [DOI] [PubMed] [Google Scholar]
- 27.Ogden BE, Hill HR. Histamine regulates lymphocyte mitogenic responses through activation of specific H1 and H2 histamine receptors. Immunology. 1980;41:107. [PMC free article] [PubMed] [Google Scholar]
- 28.Ortaldo JR, Herberman RB. Heterogeneity of NK cells. Annu Rev Immunol. 1984;2:359. doi: 10.1146/annurev.iy.02.040184.002043. [DOI] [PubMed] [Google Scholar]
- 29.Osband ME, Hamilton D, Shen YJM, Cohen E, Shlesinger M, Lavin P, Brown A, MacCaffrey R. Successful tumour immunotherapy with cimetidine in mice. Lancet. 1981;i:636. doi: 10.1016/s0140-6736(81)91554-3. [DOI] [PubMed] [Google Scholar]
- 30.Pollack SB, Hallenbeck LA. In vivo reduction of NK activity with anti NK1 serum: direct evidence of NK cells in tumor clearance. Int J Cancer. 1982;29:203. doi: 10.1002/ijc.2910290215. [DOI] [PubMed] [Google Scholar]
- 31.Pross HF, Baines MG. Spontaneous human lymphocyte mediated cytotoxicity against tumor target cells. I. The effect of malignant disease. Int J Cancer. 1976;18:593. doi: 10.1002/ijc.2910180508. [DOI] [PubMed] [Google Scholar]
- 32.Rocklin RE, Breand J, Gupta S, Good RA, Melman KL. Characterization of the human blood lymphocytes that produce a histamine induced suppressor factor. Cell Immunol. 1980;51:226. doi: 10.1016/0008-8749(80)90255-5. [DOI] [PubMed] [Google Scholar]
- 33.Ruiz-Arguelles A, Serrogy HB, Ritts RE., Jr In vitro effect of cimetidine on human cell mediated cytotoxicity. I. Inhibition of NK cell activity. Cell Immunol. 1982;69:1. doi: 10.1016/0008-8749(82)90045-4. [DOI] [PubMed] [Google Scholar]
- 34.Sahasnabudha DM, McCune CS, O'Donnell RW, Henshaw EC. Inhibition of suppressor T lymphocytes by cimetidine. J Immunol. 1987;138:2760. [PubMed] [Google Scholar]
- 35.Steinhauser EH, Doyle AT, Reed J, Kadish AN. Defective natural cytotoxicity in patients with cancer: normal number of effector cells but decreased recycling capacity in patients with advanced disease. J Immunol. 1982;129:2256. [PubMed] [Google Scholar]
- 36.Tutton PJM, Barkla DH. Comparison of the tumor inhibitory effects of three histamine H-2 receptor antagonists. Cancer Res. 1983;3:7. [PubMed] [Google Scholar]
- 37.Von Raenn J, Harris JE, Braun DP. Suppressor cell function in solid tumor cancer patients. J Clin Oncol. 1987;5:150. doi: 10.1200/JCO.1987.5.1.150. [DOI] [PubMed] [Google Scholar]