Immunomodulation of murine B16 melanoma metastasis: thymosin, thymectomy and irradiation

Thymosin, a product of the endocrine system, was used to further define the effects of immunomodulation of metastasis. Adult thymectomized C57BL/6 mice, 4 wk post-irradiation (400 R) had a decrease in the number of pulmonary metastasis (compared to controls) following tail vein injection of 5 X 10(4) B16 melanoma cells. Thymosin fraction 5 (fr. 5) administration (200 micrograms/mouse, 3 times weekly beginning 2 days post-thymectomy) returned the number of metastasis to the nonthymectomized values. Thymosin treatment of sham-operated, sham-operated irradiated, or thymectomized nonirradiated mice did not significantly elevate the number of metastases compared to the respective controls. Variant tumors which have an increase in metastasis following thymectomy and irradiation were also used. Thymosin administration reversed the effects of thymectomy in such variants, resulting in a decrease in metastasis. Metastases in thymosin-treated control mice were not significantly altered. A role for the thymus in metastasis via an endocrine product (thymosin) is suggested by these studies. Since thymosin did not increase metastasis in intact mice with tumors, further clinical trials with thymosin in cancer patients are not counterindicated by our results. These experiments confirm that thymosin fr. 5 is an important probe of the immunoendocrine events involved in tumor growth and metastasis.