[Mechanisms of enhanced accumulation of transferred LAK cells into tumor sites after chemotherapy]

Hokkaido Igaku Zasshi. 1995 May;70(3):507-17.
[Article in Japanese]

Abstract

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.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Movement
  • Female
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / therapy*
  • Humans
  • Immunotherapy, Adoptive*
  • Interleukin-2 / therapeutic use
  • Killer Cells, Lymphokine-Activated / transplantation*
  • Leukocyte Migration-Inhibitory Factors / metabolism
  • Leukocyte Migration-Inhibitory Factors / physiology
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins / therapeutic use
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology
  • Tumor Cells, Cultured

Substances

  • Interleukin-2
  • Leukocyte Migration-Inhibitory Factors
  • Recombinant Proteins
  • Transforming Growth Factor beta