Application of antibody oligostranded nucleotide conjugation strategy in polarization regulation of tumor-asso-ciated macrophages
The occurrence and development of tumors is the result of the interaction between tumor cells and their tumor micro environment(TME),which distributes a variety of stromal cells,among which tumor-associated mac-rophages(TAMs)are the most abundant.According to the type of helper T cells with which macrophages respond,po-larized macrophages can be roughly divided into M1 and M2 macrophages.In most tumors,M1 macrophages are in-volved in anti-tumor immunity,while M2 macrophages mainly play a pro-tumor role and are associated with poor prog-nosis.Recent studies have shown that during tumor development,TAMs undergo a process from an immunostimulated M1-like phenotype to an immunosuppressive M2-like phenotype,which is influenced by a variety of factors and can be reversed.This provides a new idea for tumor immunotherapy,that is,through the directional regulation of TAMs,the microenvironment of M2-like macrophages to promote tumors is reversed,and the inhibitory effect of M1-like macropha-ges on tumors is exerted.The regimen is also expected to be used in combination with immune checkpoint blockade(ICB)to enhance the therapeutic effect of ICB.siRNA-mediated gene silencing is a safe gene regulation method for humans,and has unique advantages in the regulation of TAMs.Specific antibodies have been widely used in targeted therapy for a variety of tumors due to their high selectivity.The antibody-oligonucleotide conjugates(AOCs)combine the advantages of both and are the best way to reverse M2-like macrophages in TAMs.This article mainly reviews the role and regulatory mechanism of TAMs in TME,and discusses the feasibility and application prospect of using AOC drugs to target the phenotype of TAMs and inhibit tumor development.