Inflammation and cancer: Reprogramming the immune microenvironment as an anti-cancer therapeutic strategy


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Lisa M Coussens1
1Knight Cancer Institute, Oregon Health & Sciences University, Portland, USA

Abstract

The concept that leukocytes are components of malignant tumours is not new; however, their functional involvement as promoting forces in tumour progression has only recently been appreciated. We are interested in understanding the molecular mechanisms that regulate leukocyte recruitment into neoplastic tissue, subsequent regulation those leukocytes exert on evolving cancer cells, and how malignant cells in turn respond to cytotoxic therapies. By studying transgenic mouse models of skin, lung, breast and pancreas cancer development, we have appreciated that adaptive leukocytes differentially regulate myeloid cell recruitment, activation, and behaviour, by organ-dependent mechanisms. In turn, selective myeloid cell types provide key survival factors to malignant cells, foster angiogenic programs and invariably blunt CD8+ T cell-mediated killing of tumour cells. Treatment of transgenic mice predisposed to these various cancer types with agents that selectively block adaptive/myeloid-based programs results in slowing of primary tumour growth, improved responses to chemotherapeutic drugs, and significantly diminished presence of metastatic disease. To be presented will be recent insights into organ and tissue-specific regulation of epithelial cancer development by adaptive and innate immune cells, and new studies evaluating how attenuating pro-tumour properties of myeloid cells can be exploited to enhance therapeutic responses to cytotoxic therapy.

Lisa M Coussens acknowledges generous support from the NIH/NCI, the Department of Defense Era of Hope Scholar Expansion Award, Susan G Komen Foundation, and the Breast Cancer Research Foundation.