Research Fellow Olivia Newton-John Cancer Research Institute Collingwood, Victoria, Australia
Disclosure(s):
Kok Fei Chan, PhD: No financial relationships to disclose
Introduction/Rationale: Our current work is focused on understanding the mechanisms of human γδ T-cell activation and tumor cell killing. Our group has defined the molecular aspects of the T-cell receptor (TCR)-dependent activation of Vg9Vd2+ T cells by tumors following the presentation of phosphoantigens via BTN2A1/BTN3A1 complexes. Activated human γδ T cells can undergo rapid expansion in the periphery and form up to 30% of infiltrating T cells during the onset of disease, recognize and eradicate a broad range of haematological and solid malignancies in a major histocompatibility complex (MHC)-unrestricted manner. Further, γδ T cells exhibit an inherent affinity for tumor microenvironment and can orchestrate other tumor-infiltrating immune cells for tumor cell killing. Many clinical studies to date have shown that the presence of high number of γδ T cells within tumors is strongly correlated with overall patient survival.
Methods: We isolated and expanded large numbers of human Vδ2+ γδ T cells in vitro and performed comprehensive immunophenotyping of the expanded cells.
Results: We established a preclinical humanized tumor model using NOD scid gamma (NSG) mice and showed delayed tumor growth in mice that received 4 rounds of activated human Vδ2+ γδ T cell adoptive cell transfer.
Conclusion: Hence, by understanding and harnessing the potential of activated γδ T cells, we can develop more effective combination immunotherapies for cancer patients.
