Novel post-translational modifications of protein by metabolites with immune responses and immune-related molecules in cancer immunotherapy

Tumour immunotherapy is an effective and essential treatment for cancer. However, the heterogeneity of tumours and the complex and changeable tumour immune microenvironment (TME) creates many uncertainties in the clinical application of immunotherapy, such as different responses to tumour immunotherapy and significant differences in individual efficacy. It makes anti-tumour immunotherapy face many challenges. Immunometabolism is a critical determinant of immune cell response to specific immune effector molecules, significantly affecting the effects of tumour immunotherapy. It is attributed mainly to the fact that metabolites can regulate the function of immune cells and immune-related molecules through the protein post-translational modifications (PTMs) pathway. This study systematically summarizes a variety of novel protein PTMs including acetylation, propionylation, butyrylation, succinylation, crotonylation, malonylation, glutarylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, benzoylation, lactylation and isonicotinylation in the field of tumour immune regulation and immunotherapy. In particular, we elaborate on how different PTMs in the TME can affect the function of immune cells and lead to immune evasion in cancer. Lastly, we highlight the potential treatment with the combined application of target-inhibited protein modification and immune checkpoint inhibitors (ICIs) for improved immunotherapeutic outcomes.