Small Tweaks, Major Changes: Post-Translational Modifications That Occur within M2 Macrophages in the Tumor Microenvironment

SIMPLE SUMMARY: Featuring functional diversity and plasticity, M2 macrophages have been typecasting as villain player in tumor microenvironment, propelling the growth and metastases of tumor cells and being closely related with shorter survival. Good things elude them. Why are they so bad? Trying to understand and analyze the behavior of M2 macrophages, we looked at M2 macrophages in a new perspective that is from post-translational modification (PTM) angle, proposing that it is PTMs that occur in M2 macrophages that could endow M2 macrophages with being diverse and plastic in tumor microenvironment. Given this, this review summarizes the advancement of PTMs in M2 macrophages in tumor microenvironment, to gain better understanding of M2 macrophages. ABSTRACT: The majority of proteins are subjected to post-translational modifications (PTMs), regardless of whether they occur in or after biosynthesis of the protein. Capable of altering the physical and chemical properties and functions of proteins, PTMs are thus crucial. By fostering the proliferation, migration, and invasion of cancer cells with which they communicate in the tumor microenvironment (TME), M2 macrophages have emerged as key cellular players in the TME. Furthermore, growing evidence illustrates that PTMs can occur in M2 macrophages as well, possibly participating in molding the multifaceted characteristics and physiological behaviors in the TME. Hence, there is a need to review the PTMs that have been reported to occur within M2 macrophages. Although there are several reviews available regarding the roles of M2 macrophages, the majority of these reviews overlooked PTMs occurring within M2 macrophages. Considering this, in this review, we provide a review focusing on the advancement of PTMs that have been reported to take place within M2 macrophages, mainly in the TME, to better understand the performance of M2 macrophages in the tumor microenvironment. Incidentally, we also briefly cover the advances in developing inhibitors that target PTMs and the application of artificial intelligence (AI) in the prediction and analysis of PTMs at the end of the review.