HA-1 CTLs prevent and inhibit the progression of pulmonary metastases. NOD/scid mice received human HA-1+/H-Y− MDA-MB 231 breast cancer cells intravenously on day 0 and were treated with PBS or 30 × 106 HA-1 or H-Y CTLs intravenously. (A,B) Depicted are representative examples of lungs of mice that had been treated with PBS (left), the HA-1 CTL clone 1.7 (middle), and the H-Y CTL clone 21–17 (right) on day 3 and killed on day 50. Larger pleural tumor nodules are macroscopically visible (A). Cytokeratin staining shows microtumors in the pulmonary interstitium of which some were subpleurally localized; bar represents 500 μm (B). Arrows indicate tumors. (C,D) Quantification of pulmonary tumors of mice that had been treated on day 3 and killed on day 40 (left graphs; 4 mice per group, 5 × 105 tumor cells per mouse) or on day 50 (middle graphs, 5-6 mice per group, 7.5 × 105 tumor cells per mouse); quantification of pulmonary tumors of mice that had been treated on day 40 and killed on day 50 (right graphs, 6 mice per group, 7.5 × 105 tumor cells per mouse). X-axis represents treatment with PBS, HA-1, or H-Y CTLs; y-axis, number of pleural tumor nodules visible on the intact lungs (C) or number of intrapulmonal microtumors per parallel section (D). Numbers of lung tumors were pairwise compared in different groups of mice by Mann-Whitney U test. n.s. indicates not significant. (E) Cytokeratin staining of single tumor cells in the lungs of mice 3 days after intravenous administration of MDA-MB 231 tumor cells; bar represents 50 μm. (F) CD8 staining of a pulmonary metastasis of mice that had been treated on day 40 with HA-1 CTLs and killed on day 50. Arrows indicate CD8+ CTLs; bar represents 50 μm.
