Macrophage Polarization in Chronic Lymphocytic Leukemia: Nurse-Like Cells Are the Caretakers of Leukemic Cells

Macrophages are terminally differentiated innate immune cells. Through their activation, they can be polarized towards the pro-inflammatory M1 type or the wound healing-associated, anti-inflammatory M2 type macrophages. In the tumor microenvironment (TME), M2 is the dominant phenotype and these cells are referred to as tumor-associated macrophages (TAMs). TAMs secrete cytokines and chemokines, exerting an antiapoptotic, proliferative and pro-metastatic effect on the tumor cells. TAMs can be found in many cancers, including chronic lymphocytic leukemia (CLL), where they are called nurse-like cells (NLCs). Despite the generally indolent behavior of CLL, the proportion of treatment-refractory patients is significant. As with the majority of cancers, despite significant recent progress, CLL pathogenesis is poorly understood. The emerging role of the TME in nurturing the neoplastic process warrants the investigation of macrophages as a significant pathogenetic element of tumors. In this paper, we review the current knowledge on the role of stromal macrophages in CLL.