Interleukin-2-responsive wound-infiltrating lymphocytes in surgical adjuvant cancer immunotherapy.
Wound-infiltrating lymphocytes (WIL) were assessed in murine models of localized sarcoma and carcinoma to evaluate the role of interleukin-2 (IL-2)-responsive lymphocytes in adjuvant immunotherapy. Following tumor resection, IL-2 or diluent was injected at the surgical site for 6 days. Surgical site tissues were harvested and digested in a triple enzyme mixture, and single cell suspensions were prepared. Thy 1.2+ lymphocytes were isolated by incubating cells with monoclonal anti-Thy 1.2 antibody-coated magnetic beads. Lymphocyte-bead complexes were extracted with a magnet and cultured in medium containing IL-2 (100 units/ml) for 1-3 weeks. Perioperative IL-2 immunotherapy led to a three- to four-fold increase in WIL yield. WIL from IL-2-treated mice also demonstrated enhanced cytolysis of the autologous tumor and bound to activated endothelial cells with greater avidity than did the controls. We conclude that perioperative IL-2 therapy augments the yield, as well as the cytolytic and adhesive properties, of wound-infiltrating lymphocytes.
Dubinett
S M
SM
Medical Research Service, Wadsworth Veterans Administration Medical Center, Los Angeles, California.
Patrone
L
L
Huang
M
M
Markowitz
J
J
McBride
W H
WH
Economou
J S
JS
Tobias
J
J
Kelley
D
D
Yan
D
D
Seelig
M
M
D000818:Animals; D002277:Carcinoma / Q000473:pathology* / Q000601:surgery / Q000628:therapy; D002448:Cell Adhesion / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007167:Immunotherapy; D007249:Inflammation; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000473:pathology* / Q000601:surgery / Q000628:therapy; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000473:pathology
D007155:Immunologic Factors; D007376:Interleukin-2; D011994:Recombinant Proteins