Stress-induced premature senescence activated by the SENEX gene mediates apoptosis resistance of diffuse large B-cell lymphoma via promoting immunosuppressive cells and cytokines.
Stress-induced premature senescence activated by the SENEX gene mediates apoptosis resistance of diffuse large B-cell lymphoma via promoting immunosuppressive cells and cytokines.
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DOI：
10.1002/iid3.356
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Zhai Z
中科院分区：
文献类型：
--
作者：
Wang J;Tao Q;Pan Y;Wanyan Z;Zhu F;Xu X;Wang H;Yi L;Zhou M;Zhai Z
复发难治性（r/r）弥漫性大B细胞淋巴瘤（DLBCL）的根本原因通常与细胞凋亡对抗肿瘤药物的耐药性有关。近年来有大量证据表明肿瘤细胞在化疗后可能经历应激诱导的过早衰老（SIPS），但SIPS是如何影响淋巴瘤细胞的尚无定论。52例DLBCL患者，包括6例新诊断（ND）， 17例完全缓解（CR）和29例（r/r）纳入本研究。我们使用衰老相关的β -半乳糖苷酶（SA - β - Gal）染色试剂盒进行衰老染色。通过流式细胞术（FCM）检测包括调节性T细胞（Treg）和髓源性抑制细胞（MDSC）在内的抑制性免疫细胞。用ELISA试剂盒检测分泌的细胞因子，用实时定量聚合酶链反应检测SENEX基因表达。采用40nm阿霉素体外诱导大细胞淋巴瘤SIPS模型。FCM和CCK8分别检测LY8衰老细胞的凋亡和增殖活性。通过RNA干扰使SENEX基因沉默。r/r DLBCL患者的衰老淋巴瘤细胞比例显著增加，同时Treg、MDSC及多种具有促炎和免疫抑制作用的分泌因子升高。SENEX基因在SIPS模型中显著升高。衰老的DLBCL细胞具有良好的抗凋亡能力和增殖活性，并伴有免疫抑制因子的增加。有趣的是，当我们在DLBCL细胞系中沉默SENEX基因时，结果与上述相反。由SENEX基因激活的SIPS通过促进免疫抑制细胞和细胞因子介导r/r DLBCL的凋亡抵抗。我们提出SENEX基因诱导的早衰通过促进免疫抑制细胞和细胞因子介导大B细胞淋巴瘤（DLBCL）的凋亡抵抗。
The underlying cause of relapsed and refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) is usually related to apoptosis resistance to antitumor drugs. The recent years have provided lots of evidence that tumor cells may undergo stress‐induced premature senescence (SIPS) in response to chemotherapy, but how SIPS affects lymphoma cells remains inconclusive. Fifty‐two DLBCL patients, including 6 newly diagnosed (ND), 17 complete remissions (CR), and 29 (r/r), were enrolled in this study. We used a senescence‐associated‐β‐galactosidase (SA‐β‐Gal) staining kit for senescence staining. Suppressive immune cells including regulatory T cells (Treg) and myeloid‐derived suppressor cells (MDSC) were detected by flow cytometry (FCM). Secreted cytokines were measured by ELISA Kit and SENEX gene expression was detected by a quantitative real‐time polymerase chain reaction. We used 40 nM doxorubicin to induce the SIPS model of DLBCL in vitro. Apoptosis and proliferation activity of senescent LY8 cells were respectively detected by FCM and CCK8. SENEX gene was silenced by RNA interference. The proportion of senescent lymphoma cells was significantly increased in r/r DLBCL patients, concomitant with increased Treg, MDSC, and various secreted cytokines with proinflammatory and immunosuppressive effects. The SENEX gene was significantly elevated in the SIPS model. Senescent DLBCL cells had good antiapoptotic ability and proliferative activity accompanied by increased immunosuppressive cytokines. Interestingly, when we silenced the SENEX gene in the DLBCL cell line, the results were the opposite to the above. SIPS activated by the SENEX gene mediates apoptosis resistance of r/r DLBCL via promoting immunosuppressive cells and cytokines. We propose premature senescence induced by the SENEX gene mediates apoptosis resistance of large B‐cell lymphoma (DLBCL) via promoting immunosuppressive cells and cytokines.
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影响因子：
13.1
作者：
Oshima, Junko;Sidorova, Julia M.;Monnat, Raymond J., Jr.
通讯作者：
Monnat, Raymond J., Jr.
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
11.2
作者：
Humphries, Brock;Wang, Zhishan;Yang, Chengfeng
通讯作者：
Yang, Chengfeng
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J