Cytotoxic T-Lymphocyte Antigen-4 in Colorectal Cancer: Another Therapeutic Side of Capecitabine.
Cytotoxic T-Lymphocyte Antigen-4 in Colorectal Cancer: Another Therapeutic Side of Capecitabine.
复制标题
DOI：
10.3390/cancers13102414
复制
发表时间：
2021-05-17
期刊：
影响因子：
5.2
通讯作者：
Baradaran B
中科院分区：
文献类型：
--
作者：
Derakhshani A;Hashemzadeh S;Asadzadeh Z;Shadbad MA;Rasibonab F;Safarpour H;Jafarlou V;Solimando AG;Racanelli V;Singh PK;Najafi S;Javadrashid D;Brunetti O;Silvestris N;Baradaran B
结直肠癌（CRC）开始时，正常细胞失去平衡，肿瘤在结肠或直肠的衬里形成。细胞毒性T淋巴细胞蛋白4（CTLA-4）是一种有效的抑制T细胞活化的分子。在这里，我们分析了大肠癌组织样本和细胞系中的这种分子，以揭示这种抑制分子在CRC中的作用机制。我们的结果显示CTLA-4在组织和细胞系中有增加的趋势。最后，卡培他滨作为CRC的批准药物可以抑制这种抑制分子。可以得出结论，这种抑制性分子的抑制可以重新激活CRC患者中的免疫细胞，特别是T细胞，这增强了免疫细胞对肿瘤的抵抗。 细胞毒性T淋巴细胞抗原-4（CTLA-4）是一种抑制性免疫检查点，可在肿瘤浸润淋巴细胞和结直肠癌（CRC）细胞中表达。这种免疫检查点可以减弱抗肿瘤免疫应答并促进肿瘤生长和转移。尽管卡培他滨是治疗CRC的有效化疗药物，但其对肿瘤CTLA-4表达的影响尚不清楚。在目前的研究中，我们应用GSE 110224和GSE 25070数据集来表征CRC患者中CTLA-4的表达。然后，我们使用实时PCR分析了CRC样品、HT-29、HCT-166和SW 480细胞系中的CTLA-4表达。我们的生物信息学结果突出了与邻近非肿瘤组织相比，CRC组织中CTLA-4的过表达。我们的体外研究表明，与HT-29和HCT 116细胞相比，SW 480细胞可以显著过表达CTLA-4。卡培他滨可显著下调SW 480细胞CTLA-4的表达。总体而言，卡培他滨可以抑制CRC细胞中CTLA-4的表达，并可能将免疫治疗方法与化疗方法结合起来。
Colorectal cancer (CRC) begins when normal cells turn out of balance, and a tumor is formed in the lining of the colon or rectum. Cytotoxic T-lymphocyte protein 4 (CTLA-4) is a potent molecule that could inhibit T cell activation. Here, we analyzed this molecule in the tissue samples and cell lines of colorectal cancer to reveal the mechanism of this inhibitory molecule in CRC. Our result showed an increasing trend of CTLA-4 in tissues and cell lines. Finally, capecitabine as an approved drug in CRC could suppress this inhibitory molecule. It can be concluded that the inhibition of this inhibitory molecule can re-active the immune cells, especially T cells, in CRC patients, which boosts the immune cells against the tumor. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can substantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy.
登录
查看更多内容
影响因子：
4.1
作者：
Jacobs J;Smits E;Lardon F;Pauwels P;Deschoolmeester V
通讯作者：
Deschoolmeester V
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
64.8
作者：
Twyman-Saint Victor, Christina;Rech, Andrew J.;Maity, Amit;Rengan, Ramesh;Pauken, Kristen E.;Stelekati, Erietta;Benci, Joseph L.;Xu, Bihui;Dada, Hannah;Odorizzi, Pamela M.;Herati, Ramin S.;Mansfield, Kathleen D.;Patsch, Dana;Amaravadi, Ravi K.;Schuchter, Lynn M.;Ishwaran, Hemant;Mick, Rosemarie;Pryma, Daniel A.;Xu, Xiaowei;Feldman, Michael D.;Gangadhar, Tara C.;Hahn, Stephen M.;Wherry, E. John;Vonderheide, Robert H.;Minn, Andy J.
通讯作者：
Minn, Andy J.
影响因子：
5.6
作者：
Hosseinkhani N;Derakhshani A;Kooshkaki O;Abdoli Shadbad M;Hajiasgharzadeh K;Baghbanzadeh A;Safarpour H;Mokhtarzadeh A;Brunetti O;Yue SC;Silvestris N;Baradaran B
通讯作者：
Baradaran B
DOI：
10.18502/ijaai.v19i5.4467
发表时间：
2020-10-01
影响因子：
1.5
作者：
Derakhshani, Afshin;Mollaei, Homa;Baradaran, Behzad
通讯作者：
Baradaran, Behzad