蛋白糖基化及其在当前免疫治疗策略中的作用

Proteins and associated post-translational modifications are receiving deserved attention in the search for immune therapies to combat a long list of diseases, including a number of fatal forms of cancer. Such attention has been fueled by a number of clinical results generated by numerous clinical trials, together with datasets generated by academic research. The title of this review is based on a couple of considerations: most, if not all, researched immune checkpoints are proteins, each of which can experience one or more post-translational modifications (PTMs). It is also known that among the main functions of post-translational modifications is their direct impact on protein localization. Given that most activities of known checkpoints are performed on the surface of the host cells, post-translational modifications are bound to influence the role of these proteins, both as drivers of various diseases and as therapeutic targets.

The second consideration concerns another class of proteins, which is responsible for a severe toxic reaction in the immune system following treatment with immune cell inhibitors, a reaction known as cytokine release syndrome (CRS). Cytokines are low-molecular-weight proteins, among which the key members are interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon (IFN- ). A number of clinical trials have shown that the symptoms of CRS toxicities are frequently accompanied by elevated levels of cytokines, including IL-6 and IFN- .

The recent literature suggests that we still need to know more about the biology of these proteins and the type of modifications that these key members of cytokines can experience. Such additional knowledge may contribute to more effective and safer immune cell therapy. The contribution of mass-spectrometry-based proteomics to the investigation of PTMs associated with immune checkpoints and cytokines is discussed.