Preferential Localization of Human Adherent Lymphokine-Activated Killer Cells in Tumor Microcirculation

The efficacy of adoptive immuno-therapy for solid tumors with lymphokine-activated effector cells presumably depends on the ability of these cells to localize adequately in tumor tissues. We present here the first quantitative study of the in vivo movement of fluorescently labeled adherent lymphokin...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1991-03, Vol.83 (6), p.433-437
Main Authors: Sasaki, Akihiko, Melder, Robert J., Whiteside, Theresa L., Herberman, Ronald B., Jain, Rakesh K.
Format: Article
Language:English
Subjects:
Animals
Cell Adhesion - physiology
Cell Movement - physiology
Ear, External - blood supply
Endothelium, Vascular - physiology
Humans
Interleukin-2 - pharmacology
Killer Cells, Lymphokine-Activated - cytology
Killer Cells, Lymphokine-Activated - physiology
Microcirculation
Microscopy, Fluorescence - methods
Neoplasm Transplantation
Neoplasms, Experimental - blood supply
Neoplasms, Experimental - pathology
Rabbits
Time Factors
Tumor Cells, Cultured
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Summary:The efficacy of adoptive immuno-therapy for solid tumors with lymphokine-activated effector cells presumably depends on the ability of these cells to localize adequately in tumor tissues. We present here the first quantitative study of the in vivo movement of fluorescently labeled adherent lymphokine-activated killer (A-LAK) cells. These cells were injected intra-arterially along with low-dose inter-leukin-2 into normal (mature granulation) tissue and an implant of VX2 carcinoma grown in the rabbit ear chamber. A small proportion of A-LAK cells accumulated preferentially in the tumor microcirculation in vivo because of an increased frequency of long-term adhesive interactions with the tumor vasculature. Stasis of blood flow in the tumor vasculature was observed 1to 2 days after injection. Subsequent necrosis of the tumors was observed, along with diffuse infiltrates of lymphocytes, monocytes, and granulocytes in the interstitial space within the tumor. Development of necrosis despite low ratios of effector cells to target cells suggests that in addition to direct cytotoxicity, the response to adoptive immunotherapy is mediated via the tumor vasculature. This novel mechanism for adoptive immunotherapy must be taken into account in the development of improved strategies for cancer treatment. [J Natl Cancer Inst 83:433–437, 1991]
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/83.6.433