Depression of T lymphocyte response by non-t suppressor cells in lung cancer patients.A possible prognostic value of suppressor-cell activity

Abstract

In the present study, we have utilized a suppressor-cell assay using a separated cell culture system. This system is based on the observations that the monocytedepleted and monocyte-enriched E- cells from healthy subjects act as helper cells (which are radiosensitive) to the T-lymphocyte response. Some of these two non-T cells from patients with neoplastic disease act as suppressor cells, which are radioresistant, to the T-lymphocyte response. For suppressor-cell activity of the x-irradiated monocyte-depleted and monocyte-enriched E- cells on autologous T-lymphocyte response to PHA, suppressor cell:responding cell ratio of 1:5 was utilized. The PHA response of purified T lymphocytes alone was within normal limits (≥50,000 cpm/culture) in 24 (80%) and it was depressed in only six (20%) of 30 untreated lung cancer patients. Of these six patients with depressed PHA response, five had stage III disease and only one had stage I disease. There was a helper cell activity of these two non-T cells on PHA response of T lymphocytes in each of 15 control healthy subjects and of five patients with benign pulmonary disease. In contrast, of 30 patients, 24 (80%) had a suppressor activity of monocyte-depleted E- cells with an average of 39% inhibition and 26 (87%) had a suppressor activity of monocyte-enriched E- cells with an average of 50% inhibition. Suppressor-cell activity in lung cancer patients correlated well with the extent of the disease. Five (63%) or six (75%) of eight patients with stage I and II had a suppressor activity of monocytedepleted or monocyte-enriched E- cells, respectively. On the other hand, 19 (86%) or 20 (91%) of 22 patients with stage III had a suppressor activity of monocyte-depleted or monocyte-enriched E- cells, respectively. A suppressor activity was observed in all six patients with small-cell-type lung cancer (one with stage I, one with stage II and four with stage III). In one patient with bronchioalveolar type (stage I), no suppressor cell activity was demonstrated. A suppressor-cell activity was seen in a majority (67% to 89%) of the remaining 23 patients with large cell, adenocarcinoma, and squamous cell type. In five patients with an initially significant suppressor-cell activity, the subsequent studies were performed during remission. A suppressor-cell activity of monocyte-depleted E- cells or monocyte-enriched E- cells on PHA response was significantly diminished in five or four cases, respectively, indicating the influence of tumor on the suppressor cell activity. Our data clearly suggest that one mechanism for the depression of cellmediated immunity seen in lung cancer patients may be the non-specific suppression of T lymphocyte functions by circulating suppressor cells and that the suppressor-cell activity may be of value to prognosticate the subsequent course of the disease in patients with lung cancer.