Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity

The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies.

A major component of tumor associated immune suppression is mediated by myeloid cells, especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies that were conducted through a CCSRI Innovation grant, the investigators discovered that oral treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or famotidine inhibits both primary breast tumor development and metastasis, in three distinct mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous potential to aid in effective cancer immunotherapy and may have immediate implications for cancer patients.

The objective of this investigation is to determine whether treatment with the H2 receptor antagonist ranitidine alters immune suppression, through modulation of immune cell populations.

The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers, subsets and activation status from healthy volunteers treated for 6 weeks with daily oral ranitidine.

Ranitidine is widely available and used over the counter in Canada. These drugs are widely recognized as safe, well tolerated and have very few side effects. It has been suggested that among the general population, over 10% of those over the age of 65 take such medications on a regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical studies in mice warrant further investigation into transferability to humans.

If the outcome of the current proposal proves to be viable, then these drugs could provide a safe method to reduce tumor associated immunosuppression with broad implications, both for current cancer patients and for those at high risk of developing cancer. Further to this, the outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell mediated immunotherapy.