Notably, SUMO-C2 showed significant activation of PI3K-AKT-mTOR pathway in TME, and excessive activation of the PI3K-AKT-mTOR pathway would lead to a combined phenotype of immunodeficiency and immune dysregulation (Nunes-Santos et al., 2019), which is critical for maintaining the immunosuppressive function of Tregs and (Myeloid-derived suppressor cells)MDSCs, while inhibition of the PI3K-AKT-mTOR pathway can reduce the expression of immunosuppressive factors as well as immune checkpoint ligands (O'Donnell et al., 2018). Here, AKT1 is linked to immunodeficiency disease.