The dependence of tumor neutralization on bone-marrow-derived cells

Radiosensitive host cells capable of potentiating tumor neutralization by immunocytes in normal recipients are present only in the bone marrow and not in the spleen or thymus. This was shown by selectively eliminating either the bone marrow, spleen or thymus of groups of mice and then subcutaneously injecting these animals with sensitized splenocytes and tumor cells. Bone marrow ablation was accomplished by the administration of the bone-seeking radioactive isotope 89Sr which did not reduce thymic or splenic cellularity. Sensitized splenocytes completely inhibited the growth of admixed tumor cells in normal, nude, splenectomized, or 88Sr-treated animals, but the sensitized cells were as ineffective in 89Sr-treated recipients as in 900-rad irradiated mice. Bone marrow cells of normal donors admixed with sensitized splenocytes and the sensitizing tumor cells caused a significant inhibition of tumor growth in 900-rad and 89Sr-treated mice. Therefore, the radiation-sensitive host cells that potentiate the tumor-inhibitory effect of sensitized splenocytes are unique to the marrow and, in the intact animal, apparently emigrate from this organ to interact with sensitized immunocytes at the site of tumor growth.