Abstract
Mechanisms of innate and adaptive resistance to checkpoint blockade immunotherapy are under intense investigation with a view to broadening the therapeutic potential of this form of treatment. In a recent manuscript by Zaretsky and colleagues, mutational events were identified that effectively crippled ongoing immunotherapy responses in patients treated with anti-PD-1 therapy. These results are discussed in the light of other recent and ongoing research efforts exploring both mutational and non-mutational resistance mechanisms, highlighting the critical translational importance of longitudinal tumor sampling.