Abstract
The effects of cytotoxic chemotherapy on NK cell function and on glass adherent cell regulation of NK cell function was evaluated in the peripheral blood mononuclear cells of 20 previously untreated solid tumor patients. Most of the patients studied had lung cancer and received one of four combination chemotherapy treatment regimens. In addition, one patient with colon carcinoma and one patient with melanoma were studied, each of whom received treatment with a single agent. The results demonstrated that chemotherapy exerted a differential influence on NK activity which correlated with the pretreatment NK level of function in the individual patient. In patients with depressed NK levels prior to treatment, chemotherapy augmented NK function; in patients with normal levels prior to treatment, chemotherapy depressed NK function. The effects observed appeared to be associated with the capacity of chemotherapy to influence glass adherent cell regulation of NK activity. There was no apparent correlation between the effects of chemotherapy on numbers of NK effector cells, Leu11+ cells, or latex-ingesting cells. Also, there was no correlation between the effects seen and the type of drug treatment that was administered; rather, this was dependent on the pretreatment NK level of function which in turn was associated with glass adherent cell regulation of NK function.
Keywords: Lung Cancer, Melanoma, Peripheral Blood Mononuclear Cell, Single Agent, Effector Cell
Footnotes
Supported in part by PHS Grant No. 27598
References
- 1.Bach JF. The mode of action of immunosuppressive agents. Amsterdam: North Holland; 1975. [PubMed] [Google Scholar]
- 2.Bhoopalam N, Creekmore SP, Micetich KC, Nand S, Choudhury A. Natural killer cell activity in CBDCA treated patients. Proc Am Soc Clin Oncol. 1984;3:57. [Google Scholar]
- 3.Braun DP, Harris JE. Effects of combination chemotherapy on immunoregulatory cells in the peripheral blood of solid tumor cancer patients: Correlation with rebound overshoot immune function recovery. Clin Immunol Immunopathol. 1981;20:143. doi: 10.1016/0090-1229(81)90178-1. [DOI] [PubMed] [Google Scholar]
- 4.Braun DP, Harris JE. Effect of cytotoxic antineoplastic chemotherapy on immunoregulatory leukocytes measured with monoclonal antibodies. Clin Immunol Immunopathol. 1984;33:54. doi: 10.1016/0090-1229(84)90292-7. [DOI] [PubMed] [Google Scholar]
- 5.Braun DP, Harris JE. Effects of cytotoxic chemotherapy on immune function in cancer patients. Cancer Treat Symp. 1985;1:19. [Google Scholar]
- 6.Braun DP, Harris JE, Rubenstein M. Relationship of arachidonic acid metabolism to indomethacin-sensitive immunoregulatory function and lymphocyte PGE sensitivity in peripheral blood mononuclear cells of disseminated solid tumor cancer patients. J Immunopharmacol. 1984;6(3):227. doi: 10.3109/08923978409019463. [DOI] [PubMed] [Google Scholar]
- 7.Chiu KM, Braun DP, Harris JE. Suppression of alloimmune response in normal individuals and cancer patients by indomethacin sensitive cells. Clin Res. 1981;29:735. [Google Scholar]
- 8.DeBoer 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.Forbes JT, Greco FA, Oldham rk. Natural cell mediated cytotoxicity in human tumor patients in natural cell mediated immunity against tumors. In: Herberman RB, editor. Natural cell-mediated immunity against tumors. New York: Academic Press; 1980. p. 1031. [Google Scholar]
- 10.Harris JE, Bagai RC, Steward THM. Serial monitoring of immune reactivity in cancer patients receiving chemotherapy as a means of predicting antitumor response. In: Daguillard F, editor. Proceedings of the Seventh Leukocyte Culture Conference. New York: Academic Press; 1973. p. 443. [Google Scholar]
- 11.Harris JE, Sengar D, Stewart T, Hyslop D. The effect of immunosuppressive chemotherapy on immune function in patients with malignant diesease. Cancer. 1976;37:1058. doi: 10.1002/1097-0142(197602)37:2+<1058::aid-cncr2820370813>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
- 12.Hengst JCD, Mokyr MB, Dray S. Importance of timing in cyclophosphamide therapy of MOPC-315 tumor bearing mice. Cancer Res. 1980;40:2135. [PubMed] [Google Scholar]
- 13.Hersh EM. Immunosuppressive agents. In: Sartorelli AC, Johns DG, editors. Antineoplastic and immunosuppressive agents, vol 1. Berlin: Springer-Verlag; 1974. p. 577. [Google Scholar]
- 14.Hersh EM, Whitecar JP, McCredie KB, Bodey GP, Freireich EJ. Chemotherapy, immunocompetence, immunosuppression and prognosis in acute leukemia. N Engl J Med. 1971;285:1211. doi: 10.1056/NEJM197111252852201. [DOI] [PubMed] [Google Scholar]
- 15.Mihich E, Sakurai Y, Kobayashi H. Biological responses in cancer chemotherapy. Cancer Res. 1983;43:6109. [PubMed] [Google Scholar]
- 16.Moykr MB, Dray S. Some of the advantages of curing mice bearing a large subcutaneous MOPC-315 tumor with low dose rather than a high dose of cyclophosphamide. Cancer Res. 1983;43:3112. [PubMed] [Google Scholar]
- 17.Nair MPN, Schwartz SA. Immunomodulatory effects of amphotericin-B on cellular cytotoxicity of normal human lymphocytes. Cell Immunol. 1982;70:287. doi: 10.1016/0008-8749(82)90330-6. [DOI] [PubMed] [Google Scholar]
- 18.Saijo N, Shimizu E, Shibya M, Irimajiri N, Takizawa T, Eguchi K, Shinkai T, Tominaga K, Shimabukuro Z, Taniguchi T, Hoshi A. Effect of chemotherapy on natural-killer activity and antibody-dependent cell-mediated cytotoxicity in carcinoma of the lung. Br J Cancer. 1982;46:180. doi: 10.1038/bjc.1982.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Takasugi M, Ramseyer A, Takasugi J. Decline of natural nonselective cell mediated cytotoxicity in patients with tumor progression. Cancer Res. 1977;37:413. [PubMed] [Google Scholar]
- 20.Targan SR. The dual interaction of prostaglandin E2 (PGE2) and interferon (IFN) on NK lytic activation: Enhanced capacity of effector-target lytic interactions (recycling) and blockage of pre-NK cell recruitment. J Immunol. 1981;127:1424. [PubMed] [Google Scholar]
- 21.Tilden AB, Balch CM. Indomethacin enhancement of immunocompetence in melanoma patients. Surgery. 1981;90:77. [PubMed] [Google Scholar]
- 22.Welsh RM. Natural killer cells and interferon. CRC Crit Rev Immunol. 1984;5:55. [PubMed] [Google Scholar]