Studies of the thymus in mice bearing the Lewis lung carcinoma. III. Possible mechanisms of tumor-induced thymic atrophy.

Adrenalectomy prevents thymic atrophy but not splenomegaly in mice implanted with Lewis Lung carcinoma cells. Surprisingly, the presence of the tumor does not lead to increased levels of corticosterone, which argues against an exclusive role of stress in the tumor-induced involution of the thymus. Interestingly, serum from tumor-bearing hosts in vitro displays strong cytolytic activity against normal syngeneic thymocytes. This thymocytotoxicity depends upon the stage of tumor development, i.e., the size of the local tumor, and is concomitant with the severe thymic atrophy. Treatment of donor mice with zinc chloride or excision of the local tumor, both of which have been shown to prevent this involution of the thymus, also abolishes the cytotoxic effect of the serum. The active component of the serum is a nonimmunoglobulin fraction of molecular weight greater than 25,000 Da. The possible mechanisms of tumor-dependent thymic atrophy as well as the in vivo relevance of this serum-mediated thymocytotoxicity are discussed.