Role of immune response as determinant of tumor progression in function of host age in the B16 melanoma

Aging constitutes the major cause for the development of most neoplastic diseases. However, tumors in aged people present with a lower degree of aggressiveness than in young patients. The reasons for this paradoxical behavior are not clear. We attempted to verify whether the immune system has a role in the relation between host age, immune response and tumor progression. We compared the growth rate of B16 melanoma and a highly malignant variant, the B16/Col/R, in young and aged mice that have or have not undergone splenectomy. The following results were obtained: (1) Splenectomy stimulated growth in the parental melanoma in both young and aged mice, indicating a protective role of the spleen against this tumor at all ages; (2) Spleen ablation provoked inhibition of the highly-metastatic variant growth in young mice, suggesting a stimulatory role of the spleen in this case; (3) By contrast, in aged mice inoculated with the B16/Col/R variant, splenectomy enhanced tumor growth, indicating a defensive role of the spleen. Age favors a positive host response against the aggressive clone of the melanoma. Differential host response in young versus aged mice can explain, in this tumor system, the difference in tumor progression rate as a function of age.