Modulation of Natural Killer Cell Activity by Serum from Cancer Patients: Preliminary Results of a Study of Patients with Colorectal Adenocarcinoma or Other Types of Cancer

As previously reported for natural killer (NK) cells of normal individuals, prior incubation of peripheral blood lymphocytes from cancer patients with human normal serum or monomeric immunoglobulin G reduced their subsequent capacity to kill K562 target cells in a 4-h 51Cr release assay. The NK activity of such treated effector cells was significantly inhibited only by 58% of sera from patients with colorectal adenocarcinoma (21 of 36 cases) and by 67% of sera from patients with other lymphoid or nonlymphoid solid tumors (22 of 33 cases). The cytotoxic activity of cells previously incubated with eight noninhibitory sera was even augmented relative to medium-treated peripheral blood lymphocytes (control). The 26 untreated cancer sera which did not inhibit significantly the NK activity ( I -) always developed significant inhibitory capacity upon heating at 56°C for 30 min (Δ+). An additional seven (21%) patients with colorectal carcinoma and four (27%) patients with other cancers were identified as having type II NK regulation, defined as sera with untreated inhibitory capacity ( I +) but with appreciably more inhibition after heating (Δ+). The sera of the last group of patients with colorectal adenocarcinoma (14 of 36 cases) defined as having type III NK regulation were not different from control sera isolated from normal individuals ( I + Δ-) except that they induced an inhibition greater than that caused by normal sera. The modulatory characteristics of sera from the first two categories of patients appear to be cancer associated, since the patterns I - Δ+ or I + Δ+ were observed with sera from only one of 30 patients with benign digestive diseases and two of 100 apparently healthy individuals. Preliminary results of longitudinal investigations of patients with colorectal adenocarcinoma revealed also that these patterns disappeared several months after resection of their tumor in all five tested patients, whereas the type III NK regulation found in patients with poor prognostic factors was unchanged after surgery in the other five of six patients. The three differnet categories of cancer sera identified by the functional assay of NK regulation indicated differences among our group of patients which were not paralleled by differences in levels of cytotoxic reactivity of their NK cells assayed in vitro in the absence of autologous serum. The abnormal behavior of sera from 37 (54%) patients with different types of malignant disease suggests the presence of a thermolabile serum factor which can either stimulate the activity of NK cells isolated from both cancer patients and normal donors, or protect them against the serum inhibitory factor which, in fact, are in higher amounts or have higher binding affinities as compared to those in sera of healthy donors. Since the type I of NK regulation appears to be correlated with both early stage of malignancy and a better clinical course postoperatively, the results of this study suggest that the in vivo effect of cancer patients' sera containing the putative stimulatory or protective factor may contribute to more efficient function of their circulating NK cells.