Tumor-derived interleukin (IL)-6 induced anti-tumor effect in immune-compromised hosts

Tumor-derived cytokines, such as interleukin (IL)-6, function in the context of tumor-to-host interactions, and their functions in immune-compromised hosts need to be addressed in the light of ever- increasing number of patients under immunosuppression. We studied the effects, in immune-comprised animals, of tumor-derived IL-6 on tumor growth using an experimental tumor vaccination model. Murine mammary carcinoma FM3A clone 25 (CL25) cells, which neither produce IL-6 nor express IL-6 receptors, were used. cDNA for murine IL-6 (mIL-6) was introduced to the CL25 cells, resulting in a high-producer (mIL-6H) clone. In the severe combined immune-deficient (SCID) mice, the inoculation 3 weeks earlier of mIL-6H to a dorsal flank site suppressed the growth of the CL25 cells at the opposite flank site; a tumor-derived IL-6-mediated vaccination effect occurred. In the T-cell-deficient nude mice, the inoculations 4 weeks earlier of mIL-6H suppressed the growth of CL25, but the simultaneous inoculation of these transfectants did not affect the growth of CL25. Reducing the number of inoculated transfectants or a shorter vaccination period obscured the suppressive effect. The amounts of circulating tumor-reactive immunoglobulin did not correlate with the suppressive effect. The subcutaneous injection of the anti-CD40 antibody generated a further suppression of tumor growth in the mIL-6H-inoculated, but not in the mock-inoculated, T-cell-deficient mice. In the immune-competent hosts, a suppressive effect was not observed. Natural killer (NK) activity was augmented in the spleen of mIL-6H-inoculated scid mice. This study indicated a possible vaccination effect with tumor-derived IL-6 in immune-compromised hosts.