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Immune Stimulation-Inhibition of Experimental Cancer Metastasis¹

Department of Pathology, School of Dental Medicine and Center for Oral Health Research, University of Pennsylvania, Philadelphia, Pennsylvania, 19174

The interaction of normal, tumor-bearing, nonspecifically sensitized, and immunized syngeneic lymphocytes and the B16 melanoma was tested in vivo by experimental pulmonary metastases.

Various numbers of lymphocytes were mixed and incubated with the tumor cells for 90 min on a rotating platform, and then the mixtures were injected i.v. into C57BL/6 mice. Normal, tumor-bearing, and nonspecifically sensitized lymphocytes mixed with tumor cells significantly increased the incidence of experimental metastasis. On the other hand, a high number (5000 : 1) of immunized syngeneic lymphocytes mixed with the B16 melanoma cells brought about a dramatic decrease in the incidence of subsequent pulmonary metastases. Following the in vitro incubation of tumor cells with syngeneic lymphocytes, clumping of tumor cells was observed. The relative importance of this clumping phenomenon to the outcome of experimental metastasis is discussed.

Mice that were either immunized against the B16 melanoma or thymectomized and X-irradiated demonstrated a significant decrease in incidence of experimental pulmonary metastasis following i.v. injection of tumor cells as compared to normal, thymectomized, or X-irradiated mice. The decrease in pulmonary metastases in thymectomized X-irradiated mice was completely reversible with i.v. injection of 1 x 10⁷ syngeneic tumor-bearing lymphocytes administered 24 hr prior to tumor cell injection. On the other hand, administration of 1 x 10⁸ syngeneic tumor-bearing lymphocytes brought about a significant decrease in the incidence of pulmonary metastases in all experimental groups. These results further support the hypothesis and work of Prehn and our earlier reports, that the immune response may have a dual role in its relationship to the development, progression, and perhaps the spread of cancer.

¹ Supported by USPHS Research Grants CA 12456 and DE 02623.

Received 8/24/73. Accepted 11/19/73.

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