Summary
The present study was undertaken to study natural killer (NK) cell activity in patients with colorectal cancer at peripheral and local levels. Mononuclear cells were isolated from uninvolved colorectal mucosa, tumor tissue and peripheral blood, and tested against the colon carcinoma cell line CaCo-2 and the erythroleukemia cell line K-562. Peripheral blood NK cell activity from the patients showed similar levels compared with healthy controls, whereas, mononuclear cells of tumor tissue were found to have a significantly decreased NK cell activity compared to the normal intestinal mucosa (P<0.01). No relation was found between the NK cell activity and the advancement of the disease according to the Duke's stage. Interferon-γ (IFN-γ) stimulated the NK cell activity of the mononuclear cells from blood, mucosa and tumor. However, the increase of NK cell activity after IFN-γ stimulation was lower in the tumor compared to the mucosa (P<0.02). The lectin, phytohaemagglutinin, increased the cytotoxicity of mononuclear cells from blood, mucosa and tumor to a similar level. These results suggest that patients with colorectal tumors exhibit a normal NK cell activity in peripheral blood and intestinal mucosa; however, a diminished NK cell activity exists at the tumor level. Although mononuclear cells isolated from the tumor have a normal response to lectin stimulation they show hyporesponsiveness to IFN-γ stimulation with regard to their NK cell activity.
Similar content being viewed by others
References
Aparicio-Pagés MN, Verspaget HW, Peña AS, Weterman IT, Mieremet-Ooms MAC, van der Zon JM, de Bruin PAF, Lamers CBHW (1989) Natural, lectin- and phorbol ester induced cellular cytotoxicity in Crohn's disease and ulcerative colitis. J Clin Lab Immunol (in press)
Balch CM, Tilden AB, Dougherty PA, Cloud GA, Abo T (1983) Depressed levels of granular lymphocytes with natural killer (NK) cell function in 247 cancer patients. Ann Surg 198:192
Balch CM, Dougherty PA, Cloud GA, Tilden AB (1984) Prostaglandin E2-mediated suppression of cellular immunity in colon cancer patients. Surgery 95:71
Balch CM, Tilden AB, Dougherty PA, Cloud GA, Abo T (1984) Heterogeneity of natural killer lymphocyte abnormalities in colon cancer patients. Surgery 97:63
Bland PW, Britton DC, Richens ER, Pledger JV (1981) Peripheral, mucosal, and tumour-infiltrating components of cellular immunity in cancer of the large bowel. Gut 22:744
Bull DM, Bookman MA (1977) Isolation and functional characterisation of human intestinal mucosa lymphoid cells. J Clin Invest 59:966
Ebert EC (1987) Characterization of lymphocytes found in colon cancer. Gastroenterology 92:1380
Fiochi C, Tubbs RR, Youngman KR (1985) Human intestinal mucosal mononuclear cells exhibit lymphokine-activated killer cell activity. Gastroenterology 88:625
Gibson PR, Jewell DP (1985) The nature of the natural killer (NK) cell of human intestinal mucosa and mesenteric lymph node. Clin Exp Immunol 61:160
Gibson PR, Jewell DP (1986) Local immune mechanisms in inflammatory bowel disease and colorectal carcinoma. Gastroenterology 90:12
Gibson PR, Dow EL, Selby WS, Strickland RG, Jewell DP (1984) Natural killer cells and spontaneous cell-mediated cytotoxicity in the human intestine. Clin Exp Immunol 56:438
Gibson PR, Hermanowicz A, Jewell DP (1984) Factors affecting the spontaneous cell-mediated cytotoxicity of intestinal mononuclear cells. Immunology 53:267
Herberman RB (1983) Possible role of natural killer cells in host resistance against tumors and others diseases. Clin Immunol Allerg 3:479
MacDermott RP, Franklin GO, Jenkins KM, Kodner IJ, Nash GS, Weinrieb IJ, I (1980) Investigation of antibody-dependent, lectin-induced, and spontaneous cell-mediated cytotoxic capabilities. Gastroenterology 78:47
MacDermott RP, Janice Bragdon M, Kodner IJ, Bertovich MJ (1986) Deficient cell-mediated cytotoxicity and hyporesponsiveness to interferon and mitogenic lectin activation by inflammatory bowel disease peripheral blood and intestinal mononuclear cells. Gastroenterology 90:6
Ming RH, Atlum D, Spellman CW, Imir T, Goodwin JS, strickland RG (1987) Peripheral blood mononuclear cell interleukin-2 production, receptor generation and lymphokine-activated cytotoxicity in inflammatory bowel disease. J Clin Immunol 7:59
Monson JRT, Ramsden CW, Giles GR, Brennan TG, Guillou PJ (1987) Lymphokine activated killer (LAK) cells in patients with gastrointestinal cancer. Gut 28:1420
Rabinowich H, Cohen R, Bruderman I, Steiner Z, Klajman A (1987) Functional analysis of mononuclear cells infiltrating into tumors: Lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Res 47:173
Schantz SP, Shillitoe EJ, Brown B, Campbell B (1986) Natural killer cell activity and head and neck cancer: a clinical assessment. JNCI 77:869
Shanahan F, Brogan M, Targan S (1987) Human mucosal cytotoxic effector cells. Gastroenterology 92:1951
Steinhauer EH, Doyle AT, Reed J, Kadish AS (1982) Defective natural cytotoxicity in patients with cancer: normal number of effector cells but decreased recycling capacity in patients with advanced disease. J Immunol 129:2255
Tweardy DJ, Fujiwara H, Scillian JJ, Ellner JJ (1986) Concurrent enhancement of monocyte immunoregulatory properties and effector functions by recombinant interferon-γ. Cell Immunol 100:34
van de Grind RJ, Ronteltap CPM, Gravekamp C, Monnikendam D, Bolhuis RLH (1986) Interferon-β and recombinant Il 2 can both enhance, but by different pathways, the nonspecific cytolytic potential of T3− natural killer cell-derived clones rather than that of T3+ clones. J Immunol 136:1700
Verspaget HW, Peña AS, Weterman IT, Lamers CBHW (1988) Disordered regulation of the in vitro immunoglobulin synthesis by intestinal mononuclear cells in Crohn's disease. Gut 29:503
Vose BM, Gallagher P, Moore M, Schofield PF (1981) Specific and non-specific lymphocyte cytotoxicity in colon carcinoma. Br J Cancer 44:846
Wei WZ, Malone K, Mahoney K, Heppner G (1986) Characterization of lymphocytic infiltrates in normal, preneoplastic, and neoplastic mouse mammary tissues. Cancer Res 46:2680
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Aparicio-Pagés, N.M., Verspaget, H.W., Peña, S.A. et al. Impaired local natural killer cell activity in human colorectal carcinomas. Cancer Immunol Immunother 28, 301–304 (1989). https://doi.org/10.1007/BF00205241
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205241