ABSTRACT
BACKGROUND: Zinc is an essential trace element required for different biological functions in a living body. Evaluating its concentration and effect during malignancy is important not only to assess the disease activity but also to evaluate its role in some important biological activities like immunity. METHODS: The experiments were carried out in transplanted, chemically induced and spontaneous tumors in mice. The serum zinc concentration (SZC) was determined under malignant condition and following treatment of solid tumor with anti-cancer agents. The importance of evaluating Cu/Zn ratio (CZR) was also determined. To evaluate its role in immune response during malignancy, studies were carried out on induced tumor bearing animals. RESULTS: The results showed that SZC had an inverse correlation with the progression of the disease. It was significantly reduced in all forms of malignancy, more so in spontaneous and induced forms of the disease. Extensive studies done with the solid form of induced tumor, established the importance of estimating the concentration of Zn, in addition to that of copper, in assessing the disease activity following treatment with anti-cancer agents. With regression of the tumor mass, there was a significant elevation in the SZC and depression in the serum copper concentration (SCC) compared to their levels prior to treatment. This was also reflected on the value of copper zinc ratio (CZR); with the onset of tumor regression, a significant reduction in CZR was noted in the tumor bearing animals compared to their untreated levels. As the state of 'regression' in the tumor mass was maintained for a considerable period of time following treatment with anti-cancer agents along with elevated zinc levels, we considered the role of zinc in controlling the tumor growth, indirectly. We observed that zinc is able to stimulate lymphocyte proliferation that may directly impact on the immune response of tumor bearing host. CONCLUSIONS: Zinc appears to play a role in tumor progression and regression and in stimulating lymphocyte proliferation. It is hypothesized that supplementing zinc to malignant subjects prior to and following therapeutic intervention with anti-cancer agents could help improve immune response of the host against existing tumor.
ABSTRACT
Flt3 ligand (Flt3L) therapy that expands dendritic cells in vivo in combination with local tumor radiotherapy (RT) significantly improved survival and induced a long-term tumor-specific immune response in a murine model of Lewis lung carcinoma (3LL). The irradiated tumor cells were able to significantly restimulate the splenocytes of the RT + Flt3L cohort in vitro. The restimulated splenocytes demonstrated increased cytotoxic response, lymphocytic proliferation and elevated levels of Th type I cytokines (IL-2, IL-12, IFN-gamma and TNF-alpha). The combination therapy of RT + Flt3L induced a long-term protective immunity in the disease-free animals. The protective effect was further enhanced when the disease-free animals were vaccinated with irradiated tumor cells. The vaccinated animals had significantly greater protection compared to the nonvaccinated group against subsequent challenge with 3LL cells. Taken together, these results indicate that the release of tumor antigens by irradiated dying tumors and concomitant administration of Flt3L was able to facilitate the generation of a tumor-specific long-term immune response against a poorly immunogenic tumor. This effect was further boosted by vaccination with irradiated tumor cells.
