ANTI-L-SELECTIN MONOCLONAL-ANTIBODY TREATMENT IN MICE ENHANCES TUMOR-GROWTH BY PREVENTING CTL SENSITIZATION IN PERIPHERAL LYMPH-NODES DRAINING THE TUMOR AREA

To examine the in vivo contribution of L-selectin in the sensitization of tumor-specific CTL, we investigated the effects of treatment with the anti-L-selectin monoclonal antibody (MAb) MEL-14 on the immune res ponse to Moloney-murine sarcoma virus (M-MSV)-induced tumors, which ex hibit spontaneous regression following generation of a strong virus-sp ecific CTL response. Daily systemic administration of MEL-14 for 10 da ys to M-MSV-injected mice gave rise to larger sarcomas that persisted for a longer time, compared with those arising in control mice injecte d with virus only. The enhanced tumor growth could not be attributed t o cytotoxic activity on leukocytes by MEL-14 since no reduction in the total cell number was detected in peripheral blood and spleen of MAb- treated mice. Evaluation of the immunological response in MAb-treated animals revealed a strong reduction in the generation of virus-specifi c CTL precursors (CTLp) in tumor-draining peripheral lymph nodes (PLN) 10 and 15 days after M-MSV injection, while in spleen, where lymphocy te localization is independent of L-selectin expression, CTLp generati on was only delayed. By day 20, when tumors had begun to regress, the CTLp number showed a marked increase in both spleen and local PLN, whe re naive recirculating CTL could now enter because L-selectin was no l onger down-regulated or blocked by the injected MAb. Our findings indi cate that functional inactivation of L-selectin by MEL-14 treatment pr evented migration of naive L-selectin(+) CTL through high endothelial venules (HEV) and their accumulation in PLN draining the tumor area, t hereby precluding the initiation of a tumor-specific CTL response that takes place primarily at this site. (C) 1996 Wiley-Liss, Inc.