MICROVESSEL ORIGIN AND DISTRIBUTION IN PULMONARY METASTASES OF B16 MELANOMA - IMPLICATION FOR ADOPTIVE IMMUNOTHERAPY

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 microvessel s, and infiltration by A-NK cells. The B16 melanoma metastases could b e 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/mm(2) were found in metastases of the deep-loose type, compared to approximately 400/mm(2) A-NK cells in the superficia l-loose metastases, and less than 200 A-NK cells/mm(2) in the compact subtype, regardless of its location (deep or superficial). Although th e origin (pulmonary or bronchial) of the blood supply to the metastati c subtypes (as revealed by electron microscopic analyses of lungs perf used with a lanthanum solution) did not account for this difference, t he density of microvessels in the metastatic subtypes correlated with the number of A-NK cells that localized into these metastases. The res istance of metastases of the compact type to infiltration of adoptivel y transferred effector cells might explain, in part, why adoptive immu notherapy seldom results in complete eradication of disseminated cance r.