The long-term objective of this proposed R21 exploratory study is to identify ways to exploit the now proven immunostimulatory effects of pine cone extract as an adjuvant to chemotherapy. The active component of this natural product has been identified as a lignin-polysaccharide complex with a molecular weight greater than 100 kDa. This study is designed to use the extract in combination with chemotherapy to treat established melanoma in a murine model. A primary aim of the study is to investigate different routes of administration and doses that result in antitumor effects that exceed those obtained by chemotherapy alone. Basic information about the involvement of the immune system in this process will be obtained through histology and cellular assays. The information gained throughout the study will then be used to further optimize treatment.This study relates to a very broad area of concern for human health. Successful completion of the study will provide a foundation for improving chemotherapy in melanoma. It will also suggest, due to the immunomodulating properties of the lignin-polysaccharide complex, that the adjuvant therapy can be applied to other forms of cancer. Thus, this study could potentially influence future treatments for a category of human disease that is far too common.