cGAS puts gas on anti-tumor effect of checkpoint inhibitor

This week PNAS published new article explaining mechanism of action of checkpoint inhibitors, such as anti-PDL1, in tumor immunity. It shows that cytoplasmic DNA sensor cGAS/STING pathway synergize with anti-PDL1 therapy in mouse model of melanoma.

While this study provides noteworthy observation, it is poorly done. For example, when comparing WT and KO mice (cGAS or STING KO mice), the authors did not mention if they used littermate control in these experiments.

In addition, when the authors used exogenous cGAMP (product of cGAS activity detected by STING), they did not use it on cGAS or STING KO mice as controls to verify relationship between cause and effect.   

    

In summary, the connection between DNA recognition system and checkpoint inhibitors is very interesting. Whether it is a simple generic augmentation of T cell priming or specific stimulation of tumor-specific T cells is to be seen.   

David Usharauli