Tumor-Associated Neutrophils: On their adverse and advantageous roles in solid carcinomas

Abstract

The tumor microenvironment comprises a variety of cell types, including cells of the immune system. In contrast to lymphocytes and macrophages, the role of neutrophils in the context of cancer has largely been ignored. As the most abundant leukocyte in the human body, neutrophils have an indispensable role in antimicrobial response and wound healing. Chronic inflammation observed in many types of cancer and the prominent presence of neutrophils in the infiltrate of a wide variety of solid tumors types led to the hypothesis that neutrophils may have important function in the anti-cancer immune response. Accumulating clinical and experimental studies demonstrated that Tumor-Associated Neutrophils (TANs) have a dual in cancer development. The interplay between TANs and the tumor leads to the secretion of various pro-tumoral cytokines, chemokines, growth factors and proteases by neutrophils to sustain angiogenesis, metastasis and proliferation and mediate increased accumulation of immune cells in the microenvironment. On the other hand, neutrophils can also elicit an anti-tumor response, by production of various cytotoxic factors and attraction of tumor killing immune cells. How TAN polarization is regulated and how the different neutrophil subtypes relate to each other and to the tumor is largely unknown. To gain insights into the mechanisms underlying the generation and function of these subtypes, this thesis will discuss the various roles of neutrophils in the immune response and tumor development, as well as the implications this can have on anti-cancer therapy. With the emergence of more specific markers, more physiological animal models for cancer development and more sophisticated imaging techniques, the neutrophil response to cancer can be assessed with increasing accuracy and as such further light can be shed upon the dual role of this leukocyte.