Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide

Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide

Blog Article

Abstract Background Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating immune cells.Macrophages are broadly categorized as M1 or M2 types, and TAMs have been shown to express an M2-like phenotype.TAMs promote tumor progression and contribute to resistance to chemotherapies.

Therefore, M2-like TAMs are potential targets for the cancer immunotherapy.In this study, we targeted M2-like TAMs using a hybrid peptide, MEL-dKLA, composed of melittin (MEL), which binds preferentially to M2-like TAMs, and the pro-apoptotic peptide d (KLAKLAK)2 (dKLA), which induces mitochondrial death after cell membrane penetration.Methods The M1 or M2-differentiated RAW264.

7 cells were used for mitochondrial colocalization and apoptosis test in vitro.For in vivo study, the murine Lewis lung carcinoma cells were inoculated subcutaneously in the right flank a&d ej-123 of mouse.The dKLA, MEL and MEL-dKLA peptides were intraperitoneally injected at 175 nmol/kg every 3 days.

Flow cytometry analysis of tumor-associated macrophages and immunofluorescence staining were performed to investigate the immunotherapeutic effects of MEL-dKLA.Results We showed that MEL-dKLA induced selective cell death of M2 macrophages in vitro, whereas MEL did not disrupt the mitochondrial membrane.We also showed that MEL-dKLA selectively macaron gel nail kit targeted M2-like TAMs without affecting other leukocytes, such as T cells and dendritic cells, in vivo.

These features resulted in lower tumor growth rates, tumor weights, and angiogenesis in vivo.Importantly, although both MEL and MEL-dKLA reduced numbers of CD206+ M2-like TAMs in tumors, only MEL-dKLA induced apoptosis in CD206+ M2-like TAMs, and MEL did not induce cell death.Conclusion Taken together, our study demonstrated that MEL-dKLA could be used to target M2-like TAMs as a promising cancer therapeutic agent.