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alternatively activated (M2) macrophages, by contrast, express molecules such as Arg1, CD206, and IL-10 in response to interleukin-4 (IL-4), interleukin-13 (IL-13), or IL-10 stimulation, and participate in inflammation resolution and tissue repair ( in vivo do not exist as fixed binary states, but rather more closely resemble a continuum of functions jointly shaped by tissue niches, inflammatory stages, and substrate availability, with their phenotypes being collectively determined by microenvironmental signals, metabolic reprogramming, and epigenetic regulation ( Figure 2 , classically activated M1 macrophages and alternatively activated M2 macrophages differ markedly in inducing signals, secreted factors, and functional characteristics, while M2 macrophages can be further subdivided into multiple subtypes (M2a, M2b, M2c, and M2d)

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Unfortunately, the five-year survival rate of metastatic CRC is less than 20%

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