PerspectiveCANCER

A p53-regulated immune checkpoint relevant to cancer

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Science  31 Jul 2015:
Vol. 349, Issue 6247, pp. 476-477
DOI: 10.1126/science.aac8475

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Summary

A major challenge in biomedical research is elucidating connections between stress responses within the cell and the extracellular microenvironment. This dialogue can transcend cellular life, and as such, premortem stress responses condition the mechanism through which corpses are cleared postmortem (1, 2). This implies that the reason why, and the means by which, cells die determine whether their demise ultimately triggers immune responses against dead-cell antigens (3). On page 499 of this issue, Yoon et al. (4) explore the role of p53, a major stress-elicited transcription factor and tumor suppressor protein (5, 6), in the clearance of dying cells by macrophages. The authors determine that p53 operates in a signaling pathway that protects against a systemic, life-threatening autoimmune disease encompassing ulcerative dermatitis, seizures, otitis, eye lesions, and glomerulonephritis (4, 7).