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Abstract
Excitement is growing for therapies that harness the power of patients' immune systems
to combat their diseases. One approach to immunotherapy involves engineering patients'
own T cells to express a chimeric antigen receptor (CAR) to treat advanced cancers,
particularly those refractory to conventional therapeutic agents. Although these engineered
immune cells have made remarkable strides in the treatment of patients with certain
hematologic malignancies, success with solid tumors has been limited, probably due
to immunosuppressive mechanisms in the tumor niche. In nearly all studies to date,
T cells bearing αβ receptors have been used to generate CAR T cells. In this review,
we highlight biological characteristics of γδ T cells that are distinct from those
of αβ T cells, including homing to epithelial and mucosal tissues and unique functions
such as direct antigen recognition, lack of alloreactivity, and ability to present
antigens. We offer our perspective that these features make γδ T cells promising for
use in cellular therapy against several types of solid tumors, including melanoma
and gastrointestinal cancers. Engineered γδ T cells should be considered as a new
platform for adoptive T cell cancer therapy for mucosal tumors.