PubReading [187] - T-cell invigoration to tumour burden ratio associated with anti-PD-1 response - A. Huang, J. Wherry et al

<p>Despite the success of monotherapies based on <strong>blockade</strong> of <strong>programmed cell death 1</strong> (PD-1) in human <strong>melanoma</strong>, most patients do not experience durable clinical benefit. Pre-existing <strong>T-cell infiltration</strong> and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after treatment with the PD-1-targeting antibody pembrolizumab and identify pharmacodynamic changes in circulating exhausted-phenotype CD8 T cells (Tex cells). Most of the patients demonstrated an immunological response to <strong>pembrolizumab</strong>. Clinical failure in many patients was not solely due to an inability to induce immune reinvigoration, but rather resulted from an imbalance between T-cell reinvigoration and tumour burden. The magnitude of reinvigoration of circulating Tex cells determined in relation to pretreatment tumour burden correlated with clinical response. By focused profiling of a mechanistically relevant circulating T-cell subpopulation calibrated to pretreatment <strong>disease burden</strong>, we identify a clinically accessible potential on-treatment predictor of response to PD-1 blockade.</p><p><em>doi:10.1038/nature22079 - 2017</em></p>