Tumor site-dependent differential modulation of systemic immunity in RENCA bearing mice

Renal cell carcinoma (RCC) is a highly metastatic cancer which is known to be immunogenic and responsive to immunotherapies using cytokines. The effect of tumor site (organ microenvironment) on the biologic behavior of murine RCC cell line (RENCA) was examined by observing systemic immunomodulations. Reduction of the spleen size observed in tumor bearing mice correlated with a significant decrease in splenic nucleated cell numbers. In the mice bearing RENCA cell tumors in the renal subcapsule, a significant increase of splenic T cell blastogenesis against Con-A (234% of naive control) was observed with reduction of NK activity (45% of naive control). The changes in T cell blastogenesis and NK activity observed in subcutis (s.c.) inoculated RENCA tumor bearers were less significant. However, macrophage functioning and proportions in the spleen were significantly increased only in s.c. tumor bearers. Data indicated tumor site-dependent differential modulation of systemic immunity in RENCA bearing mice which suggests that immunotherapy for RCC should consider not only the tumor but also the tumor's microenvironment.