The Paradoxical Roles of Inflammation during PD-1 Blockade in Cancer

Recent studies have reported paradoxical roles of inflammation in tumor immunity triggered by PD-1 checkpoint antibody (Ab) blockade. Here, we elaborate on this controversy and propose a new perspective that might help understand this paradox. Since inflammatory cytokines and PD-1 blockade are known to target different subsets of exhausted CD8⁺ T cells, we propose that the timing at which anti-PD-1 Ab therapy and cytokine modulation occur might determine the fate of exhausted CD8⁺ T cells and perhaps, the clinical outcome of immunotherapeutic modalities.