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Microvessel Origin and Distribution in Pulmonary Metastases of B16 Melanoma: Implication for Adoptive Immunotherapy¹

Department of Anatomy and Cell Biology, University of Göteborg, Göteborg, Sweden [U. N., B. R. J., M. L. U.]; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania [U. N., J. L. B., R. H. G., P. H. B.]; Department of Mathematics and Statistics, University of Pittsburgh, Pittsburgh, Pennsylvania [J. L. B.]; and Institute of Medical Microbiology, University of Århus, Århus, Denmark [M. E. H., P. H. B.]

To elucidate the role of tumor vascularization on the localization of adoptively transferred, interleukin 2-activated natural killer (A-NK) cells, pulmonary B16 melanoma metastases were analyzed with respect to location, morphological appearance, origin and density of microvessels, and infiltration by A-NK cells. The B16 melanoma metastases could be divided into four subtypes according to their location (superficial or deep in the lung parenchyma) and morphological appearance (compact or loose). Localization of adoptively transferred A-NK cells into the four subtypes of B16 pulmonary metastases differed significantly. More than 800 A-NK cells/mm² were found in metastases of the deep-loose type, compared to approximately 400/mm² A-NK cells in the superficial-loose metastases, and less than 200 A-NK cells/mm² in the compact subtype, regardless of its location (deep or superficial). Although the origin (pulmonary or bronchial) of the blood supply to the metastatic subtypes (as revealed by electron microscopic analyses of lungs perfused with a lanthanum solution) did not account for this difference, the density of microvessels in the metastatic subtypes correlated with the number of A-NK cells that localized into these metastases. The resistance of metastases of the compact type to infiltration of adoptively transferred effector cells might explain, in part, why adoptive immunotherapy seldom results in complete eradication of disseminated cancer.

¹ This study was supported by grants from the Swedish Cancer Society (Grant 1000), Nordic Cancer Union, the Assar Gabrielsson Research Foundation, syskonen Nilssons Research Foundation, the Danish Cancer Society (Grant 90-086), and Kanebo, Ltd., Osaka 534, Japan.

² To whom requests for reprints should be addressed, at Pittsburgh Cancer Institute, Biomedical Science Tower, W953, 200 Lothrop Street, Pittsburgh, PA 15213.

Received 4/ 3/95. Accepted 8/14/95.

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