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. 2023 May 23;14:1150705. doi: 10.3389/fimmu.2023.1150705

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Copyright © 2023 Blest and Chauveau

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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P2X7 mediated cGAMP uptake during MerTK blockade. Dying cancer cells are cleared by efferocytosis where the MerTK receptor present on tumor associated macrophages (TAMs) recognizes “eat me” signals Gas6/ProS. This leads to immunologically silent cell death by engulfment and digestion of the cellular corpse. Blockade of MerTK activity with an anti-MerTK antibody results in accumulation of dying cancer cells. Likely as a result of membrane disintegration, cGAMP and ATP are released into the tumor microenvironment. ATP activates P2X7 pore expressed by TAMs allowing cGAMP to passively move across the plasma membrane and drive type I IFN production through STING (1, 3–6, 24, 42–63).