CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression.
CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression.
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DOI：
10.1515/biol-2021-0094
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发表时间：
2021
影响因子：
2.2
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Chen Y;Li M;Cao J;Cai G;Li X;Liu Y;Chen W
淋巴瘤复发率很高，肿瘤干细胞可能是其重要机制。细胞毒性T淋巴细胞相关抗原4(CTLA-4)具有抑制抗肿瘤免疫、促进肿瘤进展的作用，但其在淋巴瘤中的作用和机制尚不清楚。在这里，我们收集了弥漫性大B细胞淋巴瘤(DLBCL)患者的淋巴瘤组织和外周血。结果显示，高危组CTLA-4表达和CD44+细胞数显著高于低危组。相关分析显示，CTLA-4的表达与淋巴瘤组织中的CD44+细胞和淋巴细胞中的调节性T(Treg)细胞呈正相关。体外实验表明，CTLA-4通过转化生长因子-β途径增加淋巴瘤干细胞的比例，促进淋巴瘤细胞的增殖和侵袭。此外，CTLA-4还能增强淋巴瘤细胞诱导的Treg细胞的增殖。动物实验表明，CTLA-4能促进移植淋巴瘤的生长。免疫组织化学结果显示，CTLA-4组Ki-67和CD44+细胞均显著增加。转化生长因子-β中和可显著阻断CTLA-4的上述作用。总之，CTLA-4通过对淋巴瘤干细胞的浓缩和免疫抑制促进了DLBCL的进展。
The recurrence rate of lymphoma is very high, and tumor stem cells may be an important mechanism. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can inhibit antitumor immunity and promote cancer progression, but its role and mechanism in lymphoma are still unclear. Here we collected lymphoma tissue and peripheral blood from patients with diffuse large B-cell lymphoma (DLBCL). Results showed that CTLA-4 expression and CD44+ cell in the high-risk group were significantly higher than that in the low-risk group. Correlation analysis showed that CTLA-4 expression positively correlated with CD44+ cell in lymphoma tissue and regulatory T (Treg) cells in lymphocytes. In vitro experiment showed that CTLA-4 increased the ratio of lymphoma stem cells, and proliferation and invasion of lymphoma cells through TGF-β pathway. Moreover, CTLA-4 enhanced the proliferation of Treg cells induced by lymphoma cells. Animal experiments showed that CTLA-4 can promote transplanted lymphoma growth. Immunohistochemistry results showed that both Ki-67 and CD44+ cells increased significantly in the CTLA-4 group. TGF-β neutralization can significantly block these effects of CTLA-4. In conclusion, CTLA-4 promoted DLBCL progression through lymphoma stem cell enrichment and immunosuppression.
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影响因子：
6.5
作者：
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通讯作者：
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Dow S