Dysfunctional States of Unconventional T cell Subsets in Cancer

J Leukoc Biol. 2023 Oct 14:qiad129. doi: 10.1093/jleuko/qiad129. Online ahead of print.ABSTRACTUnconventional T cells (UCTs) represent a promising therapeutic agent to overcome the current limitations of immunotherapies due to their universal T-cell receptors (TCRs), ability to respond directly to cytokine stimulation, and capacity to recruit and modulate conventional immune cells in the tumor microenvironment (TME). Like conventional T-cells, UCTs can enter a dysfunctional state and the functional differences associated with this state may provide insight into the discrepancies observed in their role in anti-tumor immunity in various cancers. The exhaustive signature of UCTs differs from conventional αβ T-cells and understanding the differences in the mechanisms underlying exhaustive differentiation in these cell types may aid in the discovery of new treatments to improve sustained anti-tumor responses. Ongoing clinical trials investigating therapies that leverage UCT populations have shown success in treating hematologic malignancies and reducing the immunosuppressive tumor environment. However, several hurdles remain to extend these promising results into solid tumors. Here we discuss the current knowledge on UCT function/dysfunction and consider how the incorporation of therapies that modulate UCT exhaustion may aid in overcoming the current limitations of immunotherapy. Additionally, we discuss how components of the TME alter the functions of UCTs and how these changes...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Source Type: research