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. 2020 Feb 13;11:167. doi: 10.3389/fimmu.2020.00167

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Copyright © 2020 Khan, Arooj and Wang.

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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Indirect effects of CTLA-4 blockade on NK cells. (A) Treg increase was correlated with NK cell suppression and decrease IL-2 availability to NK cells, which may be reversed with CTLA-4 blockade. (B) CTLA-4 blockade with antibodies increased CD4⁺ T-cell proliferation and IL-2 production. (C) Ipilimumab blockade of CTLA-4 on tumor cells has been reported to be associated with ADCC, TNF-α release by NK cells, and induction of the IL-2Rα chain on NK cells. (D) Ipilimumab was associated with an increased frequency of CD3⁻ CD56^dim CD16⁺ NK cells with increased TIM-3 expression. CD56^bright CD16⁻ NK cells with increased expression of p46 receptor and TRAIL have also been reported. (E) A combination of IL-2 plus ipilimumab was reported to be associated with increased NK cell infiltration of tumor, as well as a decrease in exhausted and differentiated NK cells.