Cancer is still the leading cause of death in Singapore according to the Ministry of Health Statistics. One of the new ways that is being developed in cancer therapeutics is harnessing the immune system to target cancer which is known as immunotherapy.
T cells are a type of immune cells and are key players of the immune system that are being harnessed to target cancer. One special type of T cells called γδ T cells can distinguish tumour cells from normal cells and kill them effectively. These cells recognize a range of tumour cells and exert anti-tumour abilities and have faster responses compared to the more common type of T cells called αβ T cells. This would make such cells an effective adoptive immunotherapy where these cells are primed and then transferred into a cancer patient.
However, a limitation with using such cells in adoptive immunotherapy is that they are easily exhausted and can become dysfunctional in the immune-suppressive tumour microenvironment. Hence, in this study led by A/Prof Haiyan Liu, Prof Nicholas Gascoigne and colleagues from Institute of Molecular and Cell Biology, they aimed to improve the efficacy of γδT cell-based therapy using a pre-activation of cytokine combinations (IL12/18, IL12/15/18, IL12/18/21, and IL12/15/18/21). However. only the combination of IL12/18/21 preactivated γδT cells had significant tumour growth inhibition in skin cancer and liver cancer animal models. This cytokine combination was also found to promote the proliferation of γδT cells and cytokine production, as well as the host T cell functions. Moreover, the IL12/18/21 preactivated γδT cells could overcome anti-PDL1 therapy resistance and had a synergistic effect on therapeutic outcomes. This would suggest that the IL12/18/21 preactivated γδT cells could be an effective cancer immunotherapeutic strategy combined with checkpoint blockade therapy.
