Apparent lack of immunogenicity of estrogen-induced testicular Leydig cell tumors in BALB/c mice.

Evaluating four in vivo indicators of immune response, we attempted to demonstrate immunogenic properties in transplantable malignant Leydig cell tumors (LCT) induced in BALB/c mice by chronic estrogen administration. Growing LCT failed to elicit the production either of the lymphokine migration inhibition factor by host splenocytes or of circulating antibodies detectable by indirect immunofluorescence. Delayed type hypersensitivity was evaluated in animals "sensitized" by growing tumor explants. Three to 6 weeks after complete tumor excision, 10(6) viable cells or frozen whole-cell equivalents were injected s.c. in one foot pad, and 2 days later the increase in popliteal node weight on that side was determined. Node hypertrophy of "immunized" animals in numerous experiments using many animals was no greater than that in the naive controls, and no evidence could be obtained to suggest the stimulation of T-suppressor cell activity during tumor growth. Finally, pretransplantation treatment of recipients with 400 rads total-body X-irradiation failed to increase the growth rate of four different tumor lines. Thus, although both estrogen-dependent and -independent transfer lines derived from eight different primary tumors were studied, each by several methodologies, we were unable to obtain evidence to suggest that estrogen-induced LCT in BALB/c mice evoke an immunological response while growing progressively in syngeneic hosts. These findings, plus the absence of recognizable virions in the five tumor lines studied by electron microscopy, argue against the participation of an "expressed" virus in the genesis of LCT. The apparent lack of immunogenicity is also consistent with the indefinite persistence of microscopic foci of viable, though dormant, malignant cells in estrogen-dependent LCT that have undergone complete "clinical" regression following hormone withdrawal.