Here, we noticed that R848@M2pep-MPsAFP induced a more significant increase in MHC II expression in macrophages in vivo (Fig. 4d) compared with the in vitro results (Supplementary Fig. 12c), which might be because that besides the efficient R848@M2pep-MPsAFP-induced reprogramming of M2-like TAMs, the complex tumor microenvironment, such as the R848@M2pep-MPsAFP-promoted IFNγ expression of CD8+ T cells might also contribute to the increased numbers of MHCII+ TAMs in tumor tissues49. This evidence concerns the gene IFNG and neoplasm.