TY - JOUR
T1 - Detection of a suppressive immunoregulatory factor (IRF) in the sera of sarcoma patients by enzyme‐linked immunoassay (ELISA) and correlation with clinical course
AU - Roth, Jack A.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1983/8
Y1 - 1983/8
N2 - Immunoregulatory factor (IRF) is a 70,000 molecular weight glycoprotein produced by human tumors that suppresses lymphocyte function including mitogen‐stimulated tritiated leucine (3H‐leu) and tritiated thymidine (3H‐Tdr) uptake, in vitro immunoglobulin synthesis, induction of allospecific cell‐mediated cytotoxicity, and proliferation of T‐cell growth factor‐dependent lymphocyte cultures. Antisera to IRF were produced by immunization of goats and rabbits with IRF purified by diethylaminoethyl (DEAE)‐anion exchange and affinity chromatography. Antisera specificity was demonstrated by binding to IRF but not control muscle extract in an ELISA test and by specific removal of IRF activity by antibody coupled to acrylamide beads. Using these antisera, a double antibody‐binding assay was developed to measure circulating levels of IRF and to determine its relationship to tumor growth and relevance for monitoring the clinical course of cancer patients. Quantitative autologous as well as allogeneic binding of sarcoma patients' sera to anti‐IRF antibody was demonstrated. Of five tumor extracts tested, two had immunosuppressive activity, and IRF was detected in the preoperative sera of both patients. These extracts were not suppressive and IRF was not detected in the preoperative sera of these patients. In a double‐blind study, analysis of serial serum samples from 26 sarcoma patients, 11 normal volunteers, and eight noncancer patients, demonstrated four patterns of circulating IRF: sustained high levels, increasing levels, decreasing levels, and no detectable IRF. Seven of 14 patients who eventually developed metastatic disease demonstrated sustained high or increasing levels of IRF. Eleven of 12 patients clinically free of tumor for five years or more, ten of 11 normal volunteers, and eight of eight noncancer patients had either a pattern of decreasing levels or no detectable IRF. Circulating IRF levels are correlated with the presence of tumor and may be useful in monitoring the clinical course of cancer patients.
AB - Immunoregulatory factor (IRF) is a 70,000 molecular weight glycoprotein produced by human tumors that suppresses lymphocyte function including mitogen‐stimulated tritiated leucine (3H‐leu) and tritiated thymidine (3H‐Tdr) uptake, in vitro immunoglobulin synthesis, induction of allospecific cell‐mediated cytotoxicity, and proliferation of T‐cell growth factor‐dependent lymphocyte cultures. Antisera to IRF were produced by immunization of goats and rabbits with IRF purified by diethylaminoethyl (DEAE)‐anion exchange and affinity chromatography. Antisera specificity was demonstrated by binding to IRF but not control muscle extract in an ELISA test and by specific removal of IRF activity by antibody coupled to acrylamide beads. Using these antisera, a double antibody‐binding assay was developed to measure circulating levels of IRF and to determine its relationship to tumor growth and relevance for monitoring the clinical course of cancer patients. Quantitative autologous as well as allogeneic binding of sarcoma patients' sera to anti‐IRF antibody was demonstrated. Of five tumor extracts tested, two had immunosuppressive activity, and IRF was detected in the preoperative sera of both patients. These extracts were not suppressive and IRF was not detected in the preoperative sera of these patients. In a double‐blind study, analysis of serial serum samples from 26 sarcoma patients, 11 normal volunteers, and eight noncancer patients, demonstrated four patterns of circulating IRF: sustained high levels, increasing levels, decreasing levels, and no detectable IRF. Seven of 14 patients who eventually developed metastatic disease demonstrated sustained high or increasing levels of IRF. Eleven of 12 patients clinically free of tumor for five years or more, ten of 11 normal volunteers, and eight of eight noncancer patients had either a pattern of decreasing levels or no detectable IRF. Circulating IRF levels are correlated with the presence of tumor and may be useful in monitoring the clinical course of cancer patients.
KW - ELISA
KW - immunoregulation
KW - immunosuppression
KW - sarcoma
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U2 - 10.1002/jso.2930230412
DO - 10.1002/jso.2930230412
M3 - Article
C2 - 6876804
AN - SCOPUS:0020509512
SN - 0022-4790
VL - 23
SP - 273
EP - 281
JO - Journal of surgical oncology
JF - Journal of surgical oncology
IS - 4
ER -