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. 2021 Nov 24;12:785222. doi: 10.3389/fimmu.2021.785222

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Copyright © 2021 Kaltenmeier, Yazdani, Morder, Geller, Simmons and Tohme

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Exogenous administration of NETs leads to enhanced T cell exhaustion in the TME. (A) 8-week-old B6 mice underwent subcutaneous injection of MC38 cancer cells in addition to biweekly NETs or PBS, respectively. Mice following NET injection had larger tumors at 3-4 weeks. (B, C) Markers for T cell exhaustion were analyzed by flow cytometry, these markers were significantly upregulated on T cells in tumors that received additional injection or purified NET chromatin but not PBS. (D, E) Similarly, T cells in NET injected tumors showed decreased mitochondrial activity, decreased glucose but increased lipid uptake compared to PBS injected tumors. Bar graphs represent mean +/- SEM of two independent experiments, performed with 3 mice each. *p < 0.05, **p < 0.01.