The immune armamentarium involved in cancer-associated inflammation encompasses a broad spectrum of immune cells and products.
Experimental and clinical data indicate that plasticity is a common property of most leukocyte subtypes and thus can be leveraged therapeutically. In contrast, macrophages activated through the tumor necrosis factor (TNF) receptor superfamily member CD40 become tumoricidal and deplete tumor stroma, thus enabling access by other immune cells and cytotoxic drugs and resulting in pancreatic tumor regression ( 7). These are variably referred to as M2, alternatively activated, or type 2 macrophages. Macrophages, for example, when exposed to type 2 cytokines like interleukin-4 (IL-4), express vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) and thereby enhance angiogenesis and mammary carcinoma metastasis, respectively ( 6). These paradoxical properties of leukocytes owe in part to functional plasticity of myeloid- and lymphoid-lineage cells. Although Virchow first hypothesized that cancer occurred at sites of chronic inflammation, postulating that immune cells release factors stimulating proliferation (of would-be tumor cells) ( 4), Coley successfully treated sarcomas with bacterial mixtures, for example, Coley’s toxins, leading to tumor regression, now known to be mediated by acutely activated cytotoxic immune cells ( 5). Inflammation is a hallmark of cancer wherein diverse immune cells exert either pro- or antitumor properties ( 1, 2) and affect therapeutic resistance ( 3).
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