[Mechanisms of enhanced accumulation of transferred LAK cells into tumor sites after chemotherapy].
We have previously reported that cancer chemotherapy prior to lymphokine activated-killer (LAK) cell-transfer gave synergistic increase in therapeutic effects of LAK adoptive immunotherapy on transplanted tumors, BMT-11 fibrosarcoma and 3LL lung carcinoma, in C57 BL/6 mice, and that transferred LAK cell-accumulation into tumor tissues was enhanced by treatment with anti-cancer drugs. The author tried to analyze mechanisms responsible for the enhanced LAK cell-accumulation into tumor tissues after chemotherapy by under agarose migration assay and LAK migration inhibitory assay. The author detected a chemotactic factor for LAK cells (LAK-attractant) and a migration inhibitory factor for LAK cells (LAK-MIF) in the conditioned medium of tumor tissues from mice treated with various anti-cancer drugs, which was not found in that of untreated tumor tissues. Since mRNA expression for transforming growth factor-beta 1 (TGF-beta 1) was found to enhance in tumor tissues after chemotherapy through RT-PCR, the author examined a possible participation of TGF-beta 1 as LAK-attractant in tumor tissues of mice treated with cyclophosphamide. Recombinant human TGF-beta 1 showed LAK-attractant activity, and anti-TGF-beta 1 antibody inhibited LAK-attractant activity in the conditioned medium. These findings indicate that TGF-beta 1 produced in tumor tissues of mice treated with anti-cancer drugs may be one of LAK-attractants. On the other hand, LAK-MIF activity was concentrated in the fraction of less than 3kDa which is a smaller molecule than that of TGF-beta 1. These findings suggest that both TGF-beta 1 and LAK-MIF produced in tumor tissues after chemotherapy contributed to the enhanced accumulation of transferred LAK cells into tumor tissues after the chemotherapy.
Kuramitsu
Y
Y
Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002465:Cell Movement; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000637:transplantation*; D007961:Leukocyte Migration-Inhibitory Factors / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D007961:Leukocyte Migration-Inhibitory Factors; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta