Research ArticleCancer Immunology

PD-1 suppresses the maintenance of cell couples between cytotoxic T cells and target tumor cells within the tumor

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Science Signaling  15 Sep 2020:
Vol. 13, Issue 649, eaau4518
DOI: 10.1126/scisignal.aau4518

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Keeping lymphocytes and tumor cells apart

When cytotoxic T cells enter tumors and become tumor-infiltrating lymphocytes (TILs), they lose their ability to kill target tumor cells. TILs in this state express inhibitory receptors, including PD-1, which are engaged in the tumor environment. Ambler et al. performed imaging analysis of mouse TILs ex vivo and showed that the suppressed cells had defective Ca2+ signaling, impaired cytoskeletal rearrangements, and a decreased ability to form productive contacts with their targets. Blocking PD-1 signaling in vivo, but not in vitro, restored these defects, stabilized the interactions between tumor cells and TILs, and improved cell killing.

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