Figure 2. Strategies to overcome limitations posed by the solid tumor microenvironment against CAR T cell therapy. CAR T therapy against solid tumors is challenged by the tumor microenvironment which includes immunosuppressive ligands and factors, physical barriers, and metabolites, which collectively impair T cell infiltration and function. Several strategies have been tested to overcome these challenges, such as disrupting the PD-1/PD-L1 axis, rewiring the T cell response through switch receptors, facilitating T cell trafficking through chemokine receptors and extracellular matrix degradation, improving metabolic fitness, and altering T cell function to overcome exhaustion.