However, CAR T cells must be combined with other therapies or with CAR T cells targeting multiple different antigens because of glioblastoma heterogeneity, tumor antigen loss during tumor progression, CAR T exhaustion in the TME, activation of compensatory adoptive resistance mechanisms, and upregulation of immunosuppressive factors and cells (e.g., IDO1, PD-L1, and Tregs) in the TME that are triggered after CAR T cell application. The gene discussed is CD274; the disease is glioblastoma.