Table 1.

Mechanisms of resistance to CAR T cell therapy

	Mechanisms of resistance	References
CAR T cells	Lack of expansion Lack of persistence Defective effector function (exhaustion)	[7, 8, 94] [7, 8, 94] [95, 96]
Tumor microenvironment	Impaired trafficking Metabolism/Hypoxia Immune suppression: Immunosuppressive cells (stroma, myeloid cells, regulatory T cells) Immunosuppressive cytokines (TGF-b, IL-10, IL-35)	[97–101] [102–104] [105, 106]
Tumor cells	Loss of target antigen Expression of inhibitory ligands (PD-L1 expression) Lack of costimulatory ligands (CD58 loss) Resistance to immune killing	[3–10, 12–22] [59–63] [75–77] [78–80]