Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging
文献类型：期刊论文
| 作者 | Munoz, Denise P.1; Yannone, Steven M.14; Kawahara, Misako13,14; Freund, Adam M.14; Rodier, Francis14; Campis, Judith10,14; Coppe, Jean-Philippe13,14; Daemen, Anneleen7,13; Veer, Laura J. van't13; Sun, Yu6,12 |
| 刊名 | JCI INSIGHT
 |
| 出版日期 | 2019 |
| 卷号 | 4期号:14页码:e124716 |
| ISSN号 | 0022-3565 |
| DOI | 10.1172/jci.insight.124716 |
| 文献子类 | Article |
| 英文摘要 | Cellular senescence is a tumor-suppressive mechanism that can paradoxically contribute to aging pathologies. Despite evidence of immune clearance in mouse models, it is not known how senescent cells (SnCs) persist and accumulate with age or in tumors in individuals. Here, we identify cooperative mechanisms that orchestrate the immunoevasion and persistence of normal and cancer human SnCs through extracellular targeting of natural killer receptor signaling. Damaged SnCs avoided immune recognition through MMP-dependent shedding of NKG2D ligands reinforced via paracrine suppression of NKG2D receptor-mediated immunosurveillance. These coordinated immunoediting processes were evident in residual, drug-resistant tumors from cohorts of more than 700 prostate and breast cancer patients treated with senescence-inducing genotoxic chemotherapies. Unlike in mice, these reversible senescence subversion mechanisms were independent of p53/p16 and exacerbated in oncogenic RAS-induced senescence. Critically, the p16(INK4A) tumor suppressor could disengage the senescence growth arrest from the damage-associated immune senescence program, which was manifest in benign nevus lesions, where indolent SnCs accumulated over time and preserved a non-proinflammatory tissue microenvironment maintaining NKG2D-mediated immunosurveillance. Our study shows how subpopulations of SnCs elude immunosurveillance and reveals potential secretome-targeted therapeutic strategies to selectively eliminate - and restore the clearance of - the detrimental SnCs that actively persist after chemotherapy and accumulate at sites of aging pathologies. |
| 学科主题 | Research & Experimental Medicine |
| WOS关键词 | CELLULAR SENESCENCE ; NKG2D LIGANDS ; TUMOR MICROENVIRONMENT ; SECRETORY PHENOTYPE ; IN-VIVO ; DAMAGE ; EXPRESSION ; NK ; CLEARANCE ; RESPONSES |
| 语种 | 英语 |
| WOS记录号 | WOS:000477572600003 |
| 出版者 | AMER SOC CLINICAL INVESTIGATION INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/557]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.UCSF Benioff Childrens Hosp Oakland, Swim Amer Natl Lab, Childrens Hosp, Oakland Res Inst, Oakland, CA USA; 2.Univ Montreal, Inst Canc Montreal, Montreal, PQ, Canada; 3.Univ Montreal, CRCHUM, Montreal, PQ, Canada; 4.Univ Montreal, Dept Radiol Radiooncol & Nucl Med, Montreal, PQ, Canada; 5.Cal Life Sci LLC, San Francisco, CA USA; 6.Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China; 7.Genentech Inc, Bioinformat & Computat Biol, San Francisco, CA 94080 USA; 8.Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, 229 Stanley Hall, Berkeley, CA 94720 USA; 9.Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA; 10.Buck Inst Res Aging, Novato, CA USA; |
| 推荐引用方式 GB/T 7714 | Munoz, Denise P.,Yannone, Steven M.,Kawahara, Misako,et al. Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging[J]. JCI INSIGHT,2019,4(14):e124716. |
| APA | Munoz, Denise P..,Yannone, Steven M..,Kawahara, Misako.,Freund, Adam M..,Rodier, Francis.,...&,.(2019).Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging.JCI INSIGHT,4(14),e124716. |
| MLA | Munoz, Denise P.,et al."Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging".JCI INSIGHT 4.14(2019):e124716. |
入库方式： OAI收割
来源：上海营养与健康研究所
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