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. Author manuscript; available in PMC: 2021 May 19.
Published in final edited form as: Immunity. 2020 May 19;52(5):729–731. doi: 10.1016/j.immuni.2020.04.009

Figure 1. Neutrophil Extracellular Traps Shield Tumor Cells from the Effects of Cytotoxic Immune Cells and Immunotherapies.

Figure 1.

Human neutrophils form neutrophil extracellular traps (NETs) following activation of CXCR1 and −2 receptors by chemokines secreted by tumor cells, including IL-8 and CXCL-1, −2, and −8 (top left). NETs shield tumor cells from the cytotoxic effects of anti-tumor immune cells—specifically NK cells and CD8+ T cells—which can result in increased tumor growth (top right). Blocking NET formation via pharmacological PAD4 inhibitors, DNAse-I, Pertussis-toxin (Ptx), or CXCR1 and −2 inhibitors allows tumor cell contact with cytotoxic immune cells. Teijeira et al. demonstrate NETosis blockade by PAD4 inhibition can increase the efficacy of anti-PD1 plus anti-CTLA4 immune checkpoint inhibitors—highlighting exciting potential for a new therapeutic strategy where NET blockade maximizes the effect of immunotherapy.