Immunotherapy for cancer: Promoting innate immunity

Abstract

Development of tumor over many years leads to reciprocal alterations in the host immune response and the tumor, enabling tumor growth seemingly paradoxically in the setting of necrosis and inflammation. Innate immune cells, granulocytes - neutrophils, eosinophils, basophils - and mast cells belong to the first line of defense sensing pathogen and damage associated molecular pattern (PAMPs, DAMPs) signals, initiating and modulating the subsequent inflammatory response. Nontheless, the prevailing contemporary strategies of immunotherapy for cancer have focused on the second line of the immune response, the adaptive immune response. We have determined that most highly evolved tumors in adults undergo necrosis, releasing DAMPs, promoting reactive angiogenesis, stromagenesis and reparative epithelial proliferation of the tumor cell. Means to aerobically eliminate such DAMPs by peroxidases released by innate immune effectors allows us to consider novel strategies for limiting tumor progression. Summarized here is our current understanding of acute and chronic inflammation and its impact on tumor development, the pathophysiology of immunity in cancer, and the influence of granulocytes and mast cells in this setting.