Tumor-associated macrophages (TAMs) are the most abundant immune cells within the tumor stroma and play a crucial role in tumor development. Although clinical investigations indicate that high levels of macrophage (MΦ) infiltration into tumors are associated with a poor prognosis, the exact role played by TAMs during tumor development remains unclear. The present study aimed to investigate dynamic changes in TAM major histocompatibility complex (MHC) class II expression levels and to assess the effects of these changes on tumor progression.

Significant inhibition of tumor growth in the murine hepatocellular carcinoma Hepa1-6 model was closely associated with partial TAM depletion. Strikingly, two distinct TAM subsets were found to coexist within the tumor microenvironment during Hepa1-6 tumor development. An MHC class II^hi TAM population appeared during the early phase of tumor development and was associated with tumor suppression; however, an MHC class II^low TAM population became increasingly predominant as the tumor progressed.

Tumor progression was positively correlated with increasing infiltration of the tumor tissues by MHC class II^low TAMs. Thus, targeting the transition of MΦ may be a novel strategy for drug development and immunotherapy.