Tumor-Growth Suppression in Vivo: Cooperation between Immune Lymphoid Cells Sensitized in Vitro and Nonimmune Bone Marrow Cells

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Abstract
Spleen cells from rats immunized with syngeneic (C58NT)D Gross virus-induced lymphoma cells restimulated in vitro with mitomycin C-treated (C58NT)D cells become cytotoxic to tumor targets and demonstrate an increased ability to adoptively confer antitumor immunity to nonimmune recipients. The purpose of the present studies was to determine whether nonimmune host cells participated in the local inhibition of tumor growth mediated by in vitro-activated cytotoxic cell populations. Adoptive transfer of antitumor immunity to irradiated syngeneic rats was more efficient when the recipients were reconstituted with normal bone marrow. A quantitative relationship was observed between the number of bone marrow cells administered and tumor-growth inhibition. Bone marrow cells from thymectomized, thoracic duct drained rats similarly were able to reconstitute lethally irradiated thymectomized recipients. Lymph node, thymus, or spleen cells were inactive when tested under the same conditions. Peritoneal-exudate (PE) cells contributed to decreased tumor growth in the presence or absence of sensitized lymphocytes. The results show that nonimmune bone marrow cells, although not required for tumor-growth suppression, interact synergistically with immune lymphocytes. These results suggest that in vitro-sensitized cells appear to inhibit tumor growth in vivo by at least two independent mechanisms: a direct, presumably cytotoxic effect on tumortarget cells and by indirect recruitment of a nonimmune radiosensitive bone marrow-derived host cell.

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