been recognized [52]. Although tumor-associated macrophages are an area of intense research [53], they are beyond the scope of this review. An important consideration regarding M2 phenotypes is that these states were typically elucidated in vitro following exposure to one or two stimuli. This does not represent the complex environmental milieu seen in tissue. Therefore, some investigators have cautioned against this classification into distinct subtypes and instead propose that M2 cells should be viewed as a spectrum of phenotypes [9].