Experimental observations on the significance of cell burden in tumor control

Experiments using a transplanted murine lymphosarcoma in syngeneic mice show that an initial inoculum of at least 106 tumor cells is needed to generate an immune response adequate to repel subsequent challenge from similar cells. The relationship among cell burden, dose of x radiation, and tumor control was studied. The experiments demonstrated that the number of tumor cells rejected as the result of an immunizing inoculation is approximately equivalent to the number of cells needed to initiate immunity. A correlation was established between the size of the initial injection and the probability of tumor invasion of regional lymph nodes. In addition, the existence was shown of a progressive increase in the number of tumor cells in axillary lymph nodes in mice in which the primary tumor recurs following irradiation, while in those mice in which the primary tumor is controlled, tumor cells in the axillary nodes disappear shortly after the local treatment. Several trials indicated that in this particular tumor system, the host's immunologic response will prevent the growth of 104−105 cell inocula but that larger numbers of cells overwhelm the natural defenses and grow unabated. Our evidence supports the clinical observation that moderate doses of irradiation will control subclinical tumor cell populations. In addition, it is suggested that the immune response of the host may enhance the effects of radiation not only by increasing local cell kill but also by preventing the proliferation of disseminated cells outside the irradiated volume.