Substance-P-Mediated Immunomodulation of Tumor Growth in a Murine Model

Substance P (SP) has been reported to have immunoregulatory properties including effects on many of the mediators involved in anti-tumor immunity. In this study, we investigated the effect of SP on tumor development in a murine model of melanoma. In addition, we examined the role of natural killer (NK) and T cells in SP-mediated modulation of tumor growth.Mice were implanted with mini-osmotic pumps that delivered a continuous infusion of either SP or PBS over a 14-day period. Five days following implantation, animals received K1735 melanoma cells and tumor growth was monitored. The role of NK and T cells in SP-mediated protection was examined by antibody depletion studies. To determine if cells from SP-treated animals could delay tumor growth in animals in the absence of exogenous SP infusion, splenocytes from mice treated with SP were adoptively transferred into SCID mice.In vivoSP treatment led to a significant delay in tumor growth. When animals were depleted of NK or T cells, this protective effect was lost. Adoptive transfer of cells from SP-treated animals led to a significant protective effect on tumor growth in SCID mice.Pretreatment of mice with SP provides protection against K1735 tumor growth, and this protection requires both T cells and NK cells. SP-mediated tumor protection can be transferred by the adoptive transfer of cells from SP-treated animals into animals that do not receive exogenous SP. These studies suggest a model in which in vivo SP treatment prior to tumor challenge primes immune mediators to prevent or delay tumor establishment.