M2-polarized macrophage surface receptor (M2pep receptor) (M2pep-R)

The M2pep receptor is a cell surface protein specifically expressed or overexpressed on M2-polarized macrophages and tumor-associated macrophages (TAMs). It was identified as the binding partner for the synthetic peptide M2pep (sequence: YEQDPWGVKWWY), which was discovered through subtractive phage display biopanning [1, 18]. While the exact molecular identity of the receptor remains elusive, it is characterized by its high affinity for M2pep and its ability to mediate the internalization of M2pep-conjugated cargoes, such as pro-apoptotic peptides (e.g., KLA) or siRNA-loaded nanoparticles [2, 4, 7]. In the tumor microenvironment, M2-polarized TAMs play a critical role in promoting angiogenesis, immunosuppression, and tumor progression; thus, the M2pep receptor serves as a strategic target for selective macrophage depletion or reprogramming [1, 8, 23]. Therapeutic strategies targeting this receptor aim to shift the immune landscape from a pro-tumorigenic M2 state to an anti-tumorigenic M1 state, thereby enhancing the efficacy of existing immunotherapies and inhibiting tumor growth [4, 21, 33].

Other names

M2 macrophage-targeting peptide receptorM2-polarized tumor-associated macrophage surface receptorM2pep binding siteM2-TAM receptor

Selective depletion of M2-polarized tumor-associated macrophages (TAMs) via receptor-mediated internalization of pro-apoptotic or cytotoxic agents, and reprogramming of the tumor microenvironment from an immunosuppressive M2 state to an immunostimulatory M1 state [1, 2, 10].