Improvement of phytohemagglutinin responsiveness of lymphocytes from cancer patients after washing in vitro
Mannick, J.A.; Constantian, M.; Pardrige, D.; Saporoschetz, I.; Badger, A.
Cancer Research 37(9): 3066-3070
1977
ISSN/ISBN: 0008-5472 PMID: 884664 Document Number: 110552
The in vitro response to phytohemagglutinin (PHA) stimulation of the peripheral blood lymphocytes from 23 patients with a variety of metastatic solid tissue cancers was studied after 1 washing and again after 6 washings of the lymphocytes in tissue culture medium. The response of each patient's lymphocytes was compared with that of lymphocytes from a simultaneously studied normal control individual. After 1 in vitro washing, the lymphocytes of 14 of the 23 cancer patients were suppressed in their response to PHA, at least 1 PHA dosage, as indicated by a proliferative response of < 1/2 of that of control lymphocytes (measured by incorporation of [3H]thymidine]. These suppressed cancer patients, as a group, had a significantly lower maximal stimulation in response to PHA than the control group (23,673 .+-. 5,079 cpm [counts/min] vs. 89,373 .+-. 9,725 cpm, P < 0.001), whereas 9 nonsuppressed cancer patients did not (74,146 .+-. 9,471 cpm, P > 0.3). After 6 in vitro washings, the lymphocytes of 12 of the 14 suppressed cancer patients improved in response to PHA stimulation at 1 or more dosages, as defined by an increase in proliferative response of 2 or more times that of the same cells in response to the same PHA dosage after 1 washing. By this criterion, the lymphocytes of 2 of 14 controls and 2 of 9 nonsuppressed cancer patients improved in response to PHA after 6 washings. The improvement in reponse of the suppressed cancer patient's lymphocytes after 6 washings, as compared with the controls, was highly significant (P < 0.01). The nonsuppressed cancer patients resembled the controls (P > 0.6). The nonspecific defect in lymphocyte activation noted in certain patients with advanced cancer may be caused by a suppressor substance or substances loosely associated with the lymphocyte cell membrane.