Functions of Diverse Myeloid Cells in the Tumor Micro-Environment

Myeloid cells are abundant in solid tumors and early infiltrate neoplastic lesions since the first stages of tumourigenesis, usually preceding other leukocytes (e.g. lymphocytes). (Clark et al., 2007) In the last decades there has been growing evidence that infiltrating T lymphocytes (CD3+ CD8+CD45RO+) are associated with favourable prognosis in human colorectal cancer (Laghi et al., 2009; Pages et al., 2005) melanoma, ovarian and breast cancer (Clemente et al., 1996; Mahmoud et al., 2011; Vesely et al., 2011; Zhang et al., 2003) In marked contrast, cells of the innate immunity, like myeloid cells, are most frequently associated with poor clinical outcomes. A number of studies have demonstrated that tumorassociated myeloid cells (TAMCs) have the ability to support tumor cell proliferation and invasion, activate the neo-angiogenic switch, and suppress anti-tumor immune responses. (DeNardo et al., 2009; Mantovani et al., 2004a; Martinez et al., 2009; Pollard, 2004; Qian and Pollard, 2010; Talmadge et al., 2007) Thus, in a simplified scheme, adaptive immunity is usually protective and limit tumour progression, while innate immunity favours disease development. However, research in recent years have added a further level of complexity, as components of the adaptive immunity (e.g. IL-4-producing CD4 T cells and antibodyproducing B cells) have been shown to activate innate immune cells in a pro-tumour manner. (DeNardo et al., 2009; Wang and Joyce, 2010) Therefore, the dynamic interplay between tumor-infiltrating cells of the innate and adaptive immunity is of paramount importance for the outcome of tumour progression or regression.