美国梅奥诊所儿科和青少年医学系Jan van Deursen和美国梅奥诊所分子药理学和实验治疗学系Hu Li研究组合作取得新成果。他们发现p21 产生一种生物活性分泌组，使受压细胞处于免疫监视之下。2021年10月29日，国际知名学术期刊《科学》发表了这一成果。

他们报告细胞周期抑制剂 p21 将细胞置于免疫监视之下，以建立控制细胞命运的生物计时器机制。p21 在选择的基因启动子处激活视网膜母细胞瘤蛋白 (Rb) 依赖性转录，以产生复杂的生物活性分泌组，称为 p21 激活的分泌表型 (PASP)。PASP 包括趋化因子 CXCL14，它能迅速吸引巨噬细胞。

如果细胞在 4 天内使 p21 正常化，这些巨噬细胞就会脱离，但如果 p21 诱导持续存在，它们就会极化为 M1 表型，淋巴细胞会产生细胞毒性 T 细胞反应以消除靶细胞，包括肿瘤前细胞。 因此，p21 在胁迫下同时诱导细胞增殖停滞和免疫监视。

据了解，免疫细胞识别并破坏受损细胞，以防止它们通过仍然知之甚少的机制引起癌症或其他病理。

附：英文原文

Title: p21 produces a bioactive secretome that places stressed cells under immunosurveillance

Author: Ines Sturmlechner, Cheng Zhang, Chance C. Sine, Erik-Jan van Deursen, Karthik B. Jeganathan, Naomi Hamada, Jan Grasic, David Friedman, Jeremy T. Stutchman, Ismail Can, Masakazu Hamada, Do Young Lim, Jeong-Heon Lee, Tamas Ordog, Remi-Martin Laberge, Virginia Shapiro, Darren J. Baker, Hu Li, Jan M. van Deursen

Issue&Volume: 2021-10-29

Abstract: Immune cells identify and destroy damaged cells to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report that the cell-cycle inhibitor p21 places cells under immunosurveillance to establish a biological timer mechanism that controls cell fate. p21 activates retinoblastoma protein (Rb)–dependent transcription at select gene promoters to generate a complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes the chemokine CXCL14, which promptly attracts macrophages. These macrophages disengage if cells normalize p21 within 4 days, but if p21 induction persists, they polarize toward an M1 phenotype and lymphocytes mount a cytotoxic T cell response to eliminate target cells, including preneoplastic cells. Thus, p21 concurrently induces proliferative arrest and immunosurveillance of cells under duress.

DOI: abb3420

Source: https://www.science.org/doi/10.1126/science.abb3420