Generation of lymphokine-activated killer (LAK) cell activity from malignant peritoneal effusions
Chao, T.Y.; Hwang, W.S.; Yeh, M.Y.
Proceedings of the National Science Council Republic of China. Part B Life Sciences 19(2): 92-98
1995
ISSN/ISBN: 0255-6596 PMID: 7624448 Document Number: 453903
A generation of lymphokine-activated killer (LAK) cell activities from malignant peritoneal effusions was investigated in 10 patients with abdominal carcinomatosis. Five of the 10 patients were victims of colorectal cancers, three of gastric cancers, and one each of ovarian cancer and cholangiocarcinoma. Lymphocytes, the so-called effusion associated lymphocytes (EALs), were isolated from malignant peritonea) effusions by density gradient centrifugation and the plastic adherence method, These isolated EALs were subsequently cultured in the presence of recombinant interleukin-2(rIL-2), 3,000 I.U./ml, for 30 days. Natural killer (NK) cell activities and LAK cell activities of the freshly isolated and cultured EALs were examined at 0, 7, 14, and 30 days of culture by means of a standard 51Cr-release assay using K-562, HL-60, and autologous tumor cells as target cells. The NK cell activities of the freshly isolated EALs were not detected in any of the 10 patients. The LAK activities, however, could be generated in all of them, and LAK cell activities. As far as cell growth was concerned, EALs proliferated well as long as the rIL-2 were present in the culture. Phenotypic analysis of the freshly isolated EALs revealed the presence of NK cells (22%, CD16+CD56+), T helper/inducer (18%, CD4+), T cytotoxic/suppressor (50%, CD8+), and B cells (8%, CD19+). After being cultured with rIL-2, the B lymphocytes gradually disappeared, and the T lymphocytes predominated with an increase in the percentage of T helper/inducer cells. Additional studies revealed that the major precursors of the LAK cell activities were NK cells. These results indicate that NK activity in malignant peritoneal effusions is suppressed in cancer patients, but that it can be augmented by rIL-2. When EALs are considered for the use of adoptive immunotherapy, our data suggest that it is better to isolate a large amount of EALs from voluminous effusions with short-term culturing than to proliferate EALs in vitro for a long time in order to obtain an ideal cytotoxicity against cancers.