Application of double-negative T cells in haematological malignancies: recent progress and future directions

Haematologic malignancies account for a large proportion of cancers worldwide. The high occurrence and mortality of haematologic malignancies create a heavy social burden. Allogeneic haematopoietic stem cell transplantation is widely used in the treatment of haematologic malignancies. However, graft-versus-host disease and relapse after allogeneic haematopoietic stem cell transplantation are inevitable. An emerging treatment method, adoptive cellular therapy, has been effectively used in the treatment of haematologic malignancies. T cells, natural killer (NK) cells and tumour-infiltrating lymphocytes (TILs) all have great potential in therapeutic applications, and chimeric antigen receptor T (CAR-T) cell therapy especially has potential, but cytokine release syndrome and off-target effects are common. Efficient anticancer measures are urgently needed. In recent years, double-negative T cells (CD3(+)CD4(-)CD8(-)) have been found to have great potential in preventing allograft/xenograft rejection and inhibiting graft-versus-host disease. They also have substantial ability to kill various cell lines derived from haematologic malignancies in an MHC-unrestricted manner. In addition, healthy donor expanded double-negative T cells retain their antitumour abilities and ability to inhibit graft-versus-host disease after cryopreservation under good manufacturing practice (GMP) conditions, indicating that double-negative T cells may be able to be used as an off-the-shelf product. In this review, we shed light on the potential therapeutic ability of double-negative T cells in treating haematologic malignancies. We hope to exploit these cells as a novel therapy for haematologic malignancies.

Automated summary

Haematologic malignancies are common and deadly worldwide. Current treatment methods such as allogeneic haematopoietic stem cell transplantation have limitations. Adoptive cellular therapy, especially using double-negative T cells, shows great potential in treating haematologic malignancies.