Post-translational modifications of proteins: dynamic regulatory network and therapeutic targets of tumor immune escape in pan-cancer

Post-translational modifications (PTMs) are critical regulators of protein function. Nearly two-thirds of all human proteins contain at least one PTM. These PTMs introduce covalent modifications, which modulate protein activity, location, and interactions. Further, PTMs are essential for understanding both physiological homeostasis and pathophysiology, and they play a key role in tumorigenesis and cancer development. Tumor immune evasion depends on dysregulated immune homeostasis caused by interactions between tumor cells and immune cells in the tumor microenvironment (TME). In this context, PTMs have emerged as one of the key regulators. From a pan-cancer perspective, PTMs remodel the tumor immune microenvironment through diverse mechanisms. The inability to regulate these processes is a common factor contributing to immune evasion in various cancers. It also facilitates crosstalk between tumor cells and components of TME, which in turn influences the response to immunotherapy. Because PTMs are dysregulated in cancers and can be reversed through drugs, they are attractive therapeutic targets. Small-molecule modulators of PTMs have the potential to reprogram the immune microenvironment and improve immune checkpoint blockade responses. Importantly, wide-ranging signal exchange networks between PTMs collectively increase tumoral immune phenotypic diversity and reveal new shared mechanisms of pan-cancer immune evasion. Recent studies show that the ways tumor cells change their surface proteins are driven by alterations in the tumor-immune environment. Further work could lead to strategies to treat many different cancers. Targeting PTM networks may overcome immune tolerance and significantly improve the clinical prognosis of cancer patients.