Abstract
Recently, cell-mediated immune response in malignant neoplasms has become the focus in immunotherapy against cancer. However, in leukemia, most studies on the cytotoxic potential of T cells have concentrated only on T cells that recognize peptide antigens (Ag) presented by polymorphic molecules of the major histocompatibility complex (MHC). This ignores the great potential of unconventional T cell populations, which include gamma-delta T cells (γδ), natural killer T cells (NKT), and mucosal-associated invariant T cells (MAIT). Collectively, these T cell populations can recognize lipid antigens, specially modified peptides and small molecule metabolites, in addition to having several other advantages, which can provide more effective applications in cancer immunotherapy. In recent years, these cell populations have been associated with a repertoire of anti- or protumor responses and play important roles in the dynamics of solid tumors and hematological malignancies, thus, encouraging the development of new investigations in the area. This review focuses on the current knowledge regarding the role of unconventional T cell populations in the antitumor immune response in leukemia and discusses why further studies on the immunotherapeutic potential of these cells are needed.
Highlights
Leukemia comprises a heterogeneous group of hematological neoplasms, which can be classified into lymphoblastic or myeloid leukemias and divided into acute and chronic types, depending on the affected cell type, maturation stage, and blast count, respectively [1]
While acute leukemias are characterized by a deep block in hematopoietic differentiation and result in an overproduction of immature blasts, chronic leukemias are characterized by the excessive production of partially mature differentiated cells, for example, lymphocytes in chronic lymphocytic leukemia (CLL) and granulocytes in chronic myeloid leukemia (CML) [2, 3]
A recent study by Crowther et al demonstrated that a human T cell clone potentially recognizes a specific cancer or associated metabolite, restricted to MHC-related protein 1 (MR1), and mediates the lysis of different types of cancer cells, including leukemic cells (LCs) lineages, as such, it mediated in vivo leukemia regression and conferred longer survival in mice [182]
Summary
Leukemia comprises a heterogeneous group of hematological neoplasms, which can be classified into lymphoblastic or myeloid leukemias and divided into acute and chronic types, depending on the affected cell type, maturation stage, and blast count, respectively [1]. While acute leukemias are characterized by a deep block in hematopoietic differentiation and result in an overproduction of immature blasts, chronic leukemias are characterized by the excessive production of partially mature differentiated cells, for example, lymphocytes in chronic lymphocytic leukemia (CLL) and granulocytes in chronic myeloid leukemia (CML) [2, 3] The hallmark of these neoplasms is the increase in leukemic cells (LCs) in the bone marrow (BM) and their release in the peripheral blood (PB) and in extramedullary sites [1]. Unlike MHC-reactive T cells, unconventional T cells generally show simplified patterns of the T cell antigen receptor (TCR) expression and usually target monomorphic Ag-presenting molecules and other ligands, where after their activation, they promote rapid and strong effector responses [9, 10] These T cell populations include γδ T cells, NKT cells, and MAIT cells. A better understanding of the participation of these underexplored cells in tumor dynamics may provide a basis for the development of potential immunotherapeutic strategies in the field of leukemias
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