It has long been recognized that the prognosis of patients with cutaneous T-cell lymphoma (CTCL), particularly mycosis fungoide (MF), is closely linked to tumor staging, namely patch, plaque and tumor stage presentation (1). This key clinical observation then begs the question as to what is the difference in either the malignant T cells or in the microenvironment of the tumor (ie the skin) at these various stages that accounts for these strikingly different clinical behaviours? Laying aside the characteristics of the malignant T cells themselves, which have been suggested to be derived from skin-resident memory T cells by Kupper and others (2), a large amount of clinical and experimental work over that last decade has clearly established the influence of the tumor microenvironment on tumor growth and progression (3). Although T cells in tumor microenvironment have drawn most of the attention from researchers, other immune cells play important roles in tumor immune surveillance and tolerance (4). Tumor-associated macrophages (TAMs), the most frequently found leucocyte population within the tumor microenvironment, have received recent attention because they are found in many common cancers, including Hodgkin’s lymphoma (5–7). Macrophages exhibit flexibility and plasticity in producing distinct biochemical and cytokine profiles in many types of tumors (8). At later stages of tumor progression, TAMs generally exhibit an M2-like phenotype with low IL-12, but high IL-10, expression. TAMs also produce high levels of VEGF, which would drive angiogenesis with tumors. We and other investigators have observed abundant macrophage infiltration in the skin lesions from patients with MF, the most frequent subtype of CTCL, and have associated this phenomenon with poor clinical prognosis (1, 9, 10)(Fig. 1).

Changes in the Th1 vs Th2 environment within different clinical tumor stages of mycosis fungoides have been noted previously by Asadullah and colleagues (11). They showed that an interferonc-rich environment was common in patch and plaque stage MF disease, whereas IL-10, a marker of Th2 immunity, was increased in tumor disease. A model suggesting that a switch to a Th2 predominant environment in advanced disease has been espoused in