Long-term expression changes of immune-related genes in prostate cancer after radiotherapy.
Long-term expression changes of immune-related genes in prostate cancer after radiotherapy.
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DOI：
10.1007/s00262-021-03036-w
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Coleman CN
中科院分区：
文献类型：
--
作者：
Eke I;Aryankalayil MJ;Bylicky MA;Sandfort V;Vanpouille-Box C;Nandagopal S;Graves EE;Giaccia AJ;Coleman CN
癌细胞中免疫相关基因的表达可以改变抗肿瘤免疫反应，从而影响患者的预后。放射治疗已被证明可以调节免疫相关基因依赖于分割方案。为了鉴定照射后基因表达的长期变化，用单剂量（SD，10戈伊）或10次分次（每次1戈伊）的分次方案（MF）照射PC 3（p53缺失）和LNCaP（p53野生型）前列腺癌细胞。全人类基因组阵列被用来确定基因表达在24小时和2个月后照射。免疫途径活化用Incidity Pathway Analysis（IPA）软件分析。此外，还进行了3D集落形成试验和T细胞细胞毒性试验。与PC 3相比，LNCaP具有更高的免疫原性基因的基础表达，并且更有效地被细胞毒性T细胞杀死。在这两种细胞系中，MF照射后立即导致多个免疫相关基因的增加，而在2个月SD照射对辐射诱导的基因表达有更明显的影响。免疫原性和免疫抑制基因在PC 3细胞中通过10戈伊SD照射而长期上调，但在LNCaP中不上调。与未照射对照组相比，10戈伊SD PC 3细胞中T细胞介导的细胞毒性显著增加，并且可以通过免疫检查点抑制剂治疗进一步增强。辐射以分级依赖性方式影响癌细胞中免疫相关基因的表达。了解和靶向这些变化可能是原发性前列腺癌和复发性肿瘤的一个有前途的策略。
The expression of immune-related genes in cancer cells can alter the anti-tumor immune response and thereby impact patient outcomes. Radiotherapy has been shown to modulate immune-related genes dependent on the fractionation regimen. To identify long-term changes in gene expression after irradiation, PC3 (p53 deleted) and LNCaP (p53 wildtype) prostate cancer cells were irradiated with either a single dose (SD, 10 Gy) or a fractionated regimen (MF) of 10 fractions (1 Gy per fraction). Whole human genome arrays were used to determine gene expression at 24 h and 2 months after irradiation. Immune pathway activation was analyzed with Ingenuity Pathway Analysis (IPA) software. Additionally, 3D colony formation assays and T-cell cytotoxicity assays were performed. LNCaP had a higher basal expression of immunogenic genes and were more efficiently killed by cytotoxic T-cells compared to PC3. In both cell lines, MF irradiation resulted in an increase of multiple immune-related genes immediately after irradiation, while at 2 months SD irradiation had a more pronounced effect on radiation-induced gene expression. Both immunogenic and immunosuppressive genes were upregulated in the long-term in PC3 cells by a 10 Gy SD irradiation but not in LNCaP. T cell-mediated cytotoxicity was significantly increased in 10 Gy SD PC3 cells compared to the unirradiated control and could be further enhanced by treatment with immune checkpoint inhibitors. Irradiation impacts the expression of immune-related genes in cancer cells in a fractionation-dependent manner. Understanding and targeting these changes may be a promising strategy for primary prostate cancer and recurrent tumors.
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DOI：
10.1158/1541-7786.mcr-18-0232
发表时间：
2018-12
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Eke I;Makinde AY;Aryankalayil MJ;Reedy JL;Citrin DE;Chopra S;Ahmed MM;Coleman CN
通讯作者：
Coleman CN
影响因子：
5.7
作者：
Eke I;Makinde AY;Aryankalayil MJ;Sandfort V;Palayoor ST;Rath BH;Liotta L;Pierobon M;Petricoin EF;Brown MF;Stommel JM;Ahmed MM;Coleman CN
通讯作者：
Coleman CN
DOI：
10.1016/j.mrfmmm.2010.12.003
发表时间：
2011-02-10
影响因子：
2.3
作者：
Aypar, Umut;Morgan, William F.;Baulch, Janet E.
通讯作者：
Baulch, Janet E.
影响因子：
82.9
作者：
Formenti SC;Rudqvist NP;Golden E;Cooper B;Wennerberg E;Lhuillier C;Vanpouille-Box C;Friedman K;Ferrari de Andrade L;Wucherpfennig KW;Heguy A;Imai N;Gnjatic S;Emerson RO;Zhou XK;Zhang T;Chachoua A;Demaria S
通讯作者：
Demaria S
影响因子：
--
作者：
Bloom, Jordan E.;McNeel, Douglas G.
通讯作者：
McNeel, Douglas G.