The impact of combined histamine receptor (H1 and H2) blockade and local histamine release on tumour metastasis

Drugs that interfere with histamine receptors are widely used for the treatment of disorders such as acid reflux and for the treatment of allergic diseases. However, histamine is also an important chemical for the immune system. This study will examine whether histamine blocking drugs may reduce the effective immune response to cancer, especially if such drugs are used in combination. This study will also examine if local histamine production can enhance the immune response to cancer and limit its spread throughout the body. Histamine is a chemical produced by the body, particularly by immune cells known as mast cells. It has been shown to increase both the natural, non specific (innate) immune response to cancer and the immune response that is generated in each individual when cancer develops (acquired immune response). Histamine performs these actions by binding to two major types of histamine receptors on immune cells known as H1 and H2. Dr Marshall?s group recently demonstrated that histamine release at the initial site of a growing tumour can reduce the development of metastasis. Drugs that block histamine receptors are widely used clinically and have been shown to reduce immune responses but their impact on the immune response to cancer and subsequent spread of cancer has not been well studied. The project has three objectives: 1) to examine the ability of local immune cells known as mast cells to be activated and histamine release to block the development of metastasis in two separate models of cancer spread following surgery (breast cancer and melanoma); 2) to examine the impact of blocking histamine receptors alone and in combination on cancer growth and metastasis; 3) to determine the impact of local mast cell activation or histamine receptor blockade on several critical aspects of the immune response to tumours, which might limit cancer spread. The majority of cancer deaths are due to metastatic cancer spread. Limiting or preventing cancer metastasis is a major goal in those diagnosed with early stage cancer. Dr Marshall?s study will investigate a new approach to preventing metastasis through local histamine releaseThe research will also determine if histamine receptor blocking drugs that are commonly used by many cancer patients could have an unwanted side effect of reducing effective immunity against tumours. Through both of these approaches Dr Marshall aims to reduce the burden of metastatic disease.