Spontaneous Mammary Adenocarcinoma in Mice: Influence of Thymectomy and Reconstitution with Thymus Grafts or Spleen Cells

Neonatally thymectomized C3H MTV+ (mammary tumor virus) female mice which were grafted with syngeneic thymus from either MTV+ or MTV- animals developed spontaneous mammary tumors as frequently as did sham-operated controls. Neonatally thymectomized C3H MTV+ females which were injected with spleen cells obtained from syngeneic MTV+ mice had a significant reduction in mammary tumor incidence and a prolonged latent period of tumor development. Neonatally thymectomized C3H MTV+ females which were injected with spleen cells obtained from syngeneic MTV- mice had a higher mammary tumor incidence and shorter latent period of tumor development than the neonatally thymectomized group treated with spleen cells obtained from syngeneic MTV+ mice. These results suggest that, during early life, the thymus is critical for the normal development of spontaneous mammary carcinoma. We propose three possible mechanisms to explain the role of the thymus in spontaneous mammary carcinoma in mice: ( a ) The thymus may provide a necessary site for MTV latency and/or replication. ( b ) It could be that there are either endocrine functions of the thymus or endocrine interactions between the thymus and other organs which are not yet known. ( c ) The intact thymus is necessary for a “balanced” virus-host tumor cell immunologic interaction in a process of negative adaptation (tolerance) to the virus and/or virus-induced antigen(s). In this case, development of cancer may be a result of the tolerant state. Alternatively, cancer may develop as a result of breakdown of tolerance to the virus and/or virus-induced antigen(s). Our experiments seem to favor the latter explanation since our data suggest that host immune response (enhancing antibodies) or other immunologic reaction may contribute to the development and establishment of the cancer cells.