Gamma/Delta (γδ) T Cells: The Role of the T-Cell Receptor in Diagnosis and Prognosis of Hematologic Malignancies

There are 2 types of T cells: αβ and γδ T cells, named based on the composition of the T-cell receptor. γδ T cells are rare, making up 0.5%-10% of T cells. Although most leukemias, lymphomas, and immune-mediated conditions derive from αβ T cells, a handful of rare but important diseases are generally derived from γδ T cells, particularly primary cutaneous γδ T-cell lymphoma, hepatosplenic T-cell lymphoma, and monomorphic epitheliotropic intestinal T-cell lymphoma. There are also malignancies that may evince a γδ TCR phenotype, including large granulocytic lymphocyte leukemia, T-cell acute lymphobplastic leukemia (T-ALL), and mycosis fungoides, although such cases are rare. In this article, we will review the genesis of the T-cell receptor, the role of γδ T cells, and the importance of TCR type and methods of detection and outline the evidence for prognostic significance (or lack thereof) in lymphomas of γδ T cells. We will also highlight conditions that rarely may present with a γδ TCR phenotype and assess the utility of testing for TCR type in these diseases.