Inhibition by fibrin coagulation of lung cancer cell destruction by human interleukin-2-activated killer cells.
We examined the effect of fibrin coagulation on tumor cytotoxicity mediated by human lymphokine (IL-2)-activated killer (LAK) cells. LAK cells were induced from peripheral blood mononuclear cells (MNC) by culture with recombinant IL-2 for 4 or 5 days, and LAK cell-mediated cytotoxicity against tumor cells was assessed by 51Cr release assay in the presence or absence of plasma from normal subjects and lung cancer patients. Plasma did not affect the phase of induction of LAK activity by IL-2, but dose-dependently inhibited the effector phase of LAK cell-mediated cytotoxicity against Daudi cells. Similar inhibition of LAK cell-mediated cytotoxicity was observed on pretreatment of Daudi cells and human lung cancer cell lines with human fibrinogen plus thrombin. A parallel relationship was found between the amount of fibrinogen in plasma of lung cancer patients and inhibition of LAK cytotoxicity. This inhibition was reduced by addition of anticoagulants (heparin or argatroban). These findings suggest that fibrin coagulation on tumor cells protects them from LAK cell-mediated tumor cytotoxicity in malignant lesions and that a combination of an anticoagulant drug and IL-2/LAK therapy may be effective for treatment of lung cancer patients.
Atagi
S
S
Third Department of Internal Medicine, University of Tokushima School of Medicine.
Sone
S
S
Fukuta
K
K
Ogura
T
T
D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005337:Fibrin / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008175:Lung Neoplasms / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010875:Pipecolic Acids / Q000494:pharmacology; D013449:Sulfonamides; D013917:Thrombin / Q000494:pharmacology
D000991:Antithrombins; D007376:Interleukin-2; D010875:Pipecolic Acids; D013449:Sulfonamides; D005337:Fibrin; D005340:Fibrinogen; D001120:Arginine; D013917:Thrombin; C031942:argatroban